, Volume 65, Issue 9, pp 1239–1282 | Cite as

Herb-Drug Interactions

A Literature Review
  • Zeping Hu
  • Xiaoxia Yang
  • Paul Chi Lui Ho
  • Sui Yung Chan
  • Paul Wan Sia Heng
  • Eli Chan
  • Wei Duan
  • Hwee Ling Koh
  • Shufeng ZhouEmail author
Review Article


Herbs are often administered in combination with therapeutic drugs, raising the potential of herb-drug interactions. An extensive review of the literature identified reported herb-drug interactions with clinical significance, many of which are from case reports and limited clinical observations.

Cases have been published reporting enhanced anticoagulation and bleeding when patients on long-term warfarin therapy also took Salvia miltiorrhiza (danshen). Allium sativum (garlic) decreased the area under the plasma concentration-time curve (AUC) and maximum plasma concentration of saquinavir, but not ritonavir and paracetamol (acetaminophen), in volunteers. A. sativum increased the clotting time and international normalised ratio of warfarin and caused hypoglycaemia when taken with chlorpropamide. Ginkgo biloba (ginkgo) caused bleeding when combined with warfarin or aspirin (acetylsalicylic acid), raised blood pressure when combined with a thiazide diuretic and even caused coma when combined with trazodone in patients. Panax ginseng (ginseng) reduced the blood concentrations of alcohol (ethanol) and warfarin, and induced mania when used concomitantly with phenelzine, but ginseng increased the efficacy of influenza vaccination. Scutellaria baicalensis (huangqin) ameliorated irinotecan-induced gastrointestinal toxicity in cancer patients.

Piper methysticum (kava) increased the ‘off’ periods in patients with parkinsonism taking levodopa and induced a semicomatose state when given concomitantly with alprazolam. Kava enhanced the hypnotic effect of alcohol in mice, but this was not observed in humans. Silybum marianum (milk thistle) decreased the trough concentrations of indinavir in humans. Piperine from black (Piper nigrum Linn) and long (P. longum Linn) peppers increased the AUC of phenytoin, propranolol and theophylline in healthy volunteers and plasma concentrations of rifamipicin (rifampin) in patients with pulmonary tuberculosis. Eleutheroccus senticosus (Siberian ginseng) increased the serum concentration of digoxin, but did not alter the pharmacokinetics of dextromethorphan and alprazolam in humans. Hypericum perforatum (hypericum; St John’s wort) decreased the blood concentrations of ciclosporin (cyclosporin), midazolam, tacrolimus, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline, but did not alter the pharmacokinetics of carbamazepine, pravastatin, mycophenolate mofetil and dextromethorphan. Cases have been reported where decreased ciclosporin concentrations led to organ rejection. Hypericum also caused breakthrough bleeding and unplanned pregnancies when used concomitantly with oral contraceptives. It also caused serotonin syndrome when used in combination with selective serotonin reuptake inhibitors (e.g. sertraline and paroxetine).

In conclusion, interactions between herbal medicines and prescribed drugs can occur and may lead to serious clinical consequences. There are other theoretical interactions indicated by preclinical data. Both pharmacokinetic and/or pharmacodynamic mechanisms have been considered to play a role in these interactions, although the underlying mechanisms for the altered drug effects and/or concentrations by concomitant herbal medicines are yet to be determined. The clinical importance of herb-drug interactions depends on many factors associated with the particular herb, drug and patient. Herbs should be appropriately labeled to alert consumers to potential interactions when concomitantly used with drugs, and to recommend a consultation with their general practitioners and other medical carers.



The authors appreciate the support by the National University of Singapore Academic Research Funds.

The authors have provided no information on conflicts of interest directly relevant to the content of this review.


  1. 1.
    Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs 2001; 61(15): 2163–75PubMedCrossRefGoogle Scholar
  2. 2.
    Fugh-Berman A. Herbal medicinals: selected clinical considerations, focusing on known or potential drug-herb interactions. Arch Intern Med 1999; 159(16): 1957–8PubMedCrossRefGoogle Scholar
  3. 3.
    Fugh-Berman A. Herb-drug interactions. Lancet 2000; 355(9198): 134–8PubMedCrossRefGoogle Scholar
  4. 4.
    Fugh-Berman A, Ernst E. Herb-drug interactions: review and assessment of report reliability. Br J Clin Pharmacol 2001; 52(5): 587–95PubMedCrossRefGoogle Scholar
  5. 5.
    Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health System Pharm 2000; 57(13): 1221–7Google Scholar
  6. 6.
    Elvin-Lewis M. Should we be concerned about herbal remedies. J Ethnopharmacol 2001; 75(2–3): 141–64PubMedCrossRefGoogle Scholar
  7. 7.
    Wilkinson GR. The effects of diet, aging and disease-states on presystemic elimination and oral drug bioavailability in humans. Adv Drug Deliv Rev 1997; 27(2–3): 129–59PubMedCrossRefGoogle Scholar
  8. 8.
    Evans AM. Influence of dietary components on the gastrointestinal metabolism and transport of drugs. Ther Drug Monit 2000; 22(1): 131–6PubMedCrossRefGoogle Scholar
  9. 9.
    Ioannides C. Pharmacokinetic interactions between herbal remedies and medicinal drugs. Xenobiotica 2002; 32(6): 451–78PubMedCrossRefGoogle Scholar
  10. 10.
    Zhou SF, Gao YH, Wen QJ, et al. Interactions of herbs with cytochrome P450. Drug Metab Rev 2003; 35(1): 35–98PubMedCrossRefGoogle Scholar
  11. 11.
    Walter-Sack I, Klotz U. Influence of diet and nutritional status on drug metabolism. Clin Pharmacokinet 1996; 31: 47–64PubMedCrossRefGoogle Scholar
  12. 12.
    Kolars JC, Awni WM, Merion RM, et al. First-pass metabolism of cyclosporin by the gut. Lancet 1991; 338: 1488–90PubMedCrossRefGoogle Scholar
  13. 13.
    Paine MF, Shen DD, Kunze KL, et al. First-pass metabolism of midazolam by the human intestine. Clin Pharmacol Ther 1996; 60: 14–24PubMedCrossRefGoogle Scholar
  14. 14.
    Kim RB, Fromm MF, Wandel C, et al. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 1998; 101(2): 289–94PubMedCrossRefGoogle Scholar
  15. 15.
    Fromm MF, Busse D, Kroemer HK, et al. Differential induction of prehepatic and hepatic metabolism of verapamil by rifampin. Hepatology 1996; 24: 796–801PubMedCrossRefGoogle Scholar
  16. 16.
    Greiner B, Eichelbaum M, Fritz P, et al. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J Clin Invest 1999; 104: 147–53PubMedCrossRefGoogle Scholar
  17. 17.
    Westphal K, Weinbrenner A, Zschiesche M, et al. Induction of P-glycoprotein by rifampin increases intestinal secretion of talinolol in human beings: a new type of drug/drug interaction. Clin Pharmacol Ther 2000; 68: 345–55PubMedCrossRefGoogle Scholar
  18. 18.
    Eisenberg DM, Kessler RC, Foster C, et al. Unconventional medicine in the United States: prevalence, costs, and patterns of use. N Engl J Med 1993; 328: 246–52PubMedCrossRefGoogle Scholar
  19. 19.
    Goldman P. Herbal medicines today and the roots of modern pharmacology. Ann Intern Med 2001; 135 (8 Pt 1): 594–600PubMedGoogle Scholar
  20. 20.
    Shaw D, Leon C, Kolev S, et al. Traditional remedies and food supplements: a 5-year toxicological study (1991–1995). Drug Saf 1997; 17(5): 342–56PubMedCrossRefGoogle Scholar
  21. 21.
    WHO. WHO monographs on selected medicinal plants. Vol. 2. Geneva: World Health Organization, 2002Google Scholar
  22. 22.
    WHO. WHO monographs on selected medicinal plants. Vol. 1. Geneva: World Health Organization, 1999Google Scholar
  23. 23.
    Hoffmann D. The information sourcebook of herbal medicine. Freedom (CA): Crossing Press, 1994Google Scholar
  24. 24.
    Ernst E. Herbal medicine: a concise overview for professionals. Boston (MA): Butterworth-Heinemann, 1999Google Scholar
  25. 25.
    Ross IA. Medicinal plants of the world: chemical constituents, traditional, and modern medicinal uses. Totowa (NJ): Humana Press, 2001Google Scholar
  26. 26.
    Fetrow CW, Avila JR. The complete guide to herbal medicines. Springhouse (PA): Springhouse Corp., 2000Google Scholar
  27. 27.
    Huang KC. The pharmacology of Chinese herbs. Boca Raton (FL): CRC Press, 1998CrossRefGoogle Scholar
  28. 28.
    Yang YF. Chinese herbal medicines: comparisons and characteristics. Edinburgh: Churchill Livingstone, 2002Google Scholar
  29. 29.
    Izzo AA, Borrelli F, Capasso R. Herbal medicine: the dangers of drug interaction. Trends Pharmacol Sci 2002; 23(8): 358–91PubMedCrossRefGoogle Scholar
  30. 30.
    Scott GN, Elmer GW. Update on natural product-drug interactions. Am J Health Syst Pharm 2002; 59(4): 339–47PubMedGoogle Scholar
  31. 31.
    Klepser TB, Klepser ME. Unsafe and potentially safe herbal therapies. Am J Health Syst Pharm 1999; 56(2): 125–38PubMedGoogle Scholar
  32. 32.
    Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. J Clin Pharm Ther 2002; 27(6): 391–401PubMedCrossRefGoogle Scholar
  33. 33.
    Brazier NC, Levine MA. Drug-herb interaction among commonly used conventional medicines: a compendium for health care professionals. Am J Ther 2003; 10(3): 163–9PubMedCrossRefGoogle Scholar
  34. 34.
    Zhou S, Chan E, Pan SQ, et al. Pharmacokinetic interactions of drugs with St John’s wort. J Psychopharmacol 2004; 18(2): 262–76PubMedCrossRefGoogle Scholar
  35. 35.
    Izzo AA, Di Carlo G, Borrelli F, et al. Cardiovascular pharmacotherapy and herbal medicines: the risk of drug interaction. Int J Cardiol 2005; 98(1): 1–14PubMedCrossRefGoogle Scholar
  36. 36.
    Sparreboom A, Cox MC, Acharya MR, et al. Herbal remedies in the United States: potential adverse interactions with anti-cancer agents. J Clin Oncol 2004; 22(12): 2489–503PubMedCrossRefGoogle Scholar
  37. 37.
    Izzo AA. Herb-drug interactions: an overview of the clinical evidence. Fundam Clin Pharmacol 2005; 19(1): 1–16PubMedCrossRefGoogle Scholar
  38. 38.
    Harris JC, Cottrell SL, Plummer S, et al. Antimicrobial properties of Allium sativum (garlic). Appl Microbiol Biotechnol 2001; 57(3): 282–6PubMedCrossRefGoogle Scholar
  39. 39.
    Kyo E, Uda N, Kasuga S, et al. Immunomodulatory effects of aged garlic extract. J Nutr 2001; 131(3s): S1075–9Google Scholar
  40. 40.
    Standish LJ, Greene KB, Bain S, et al. Alternative medicine use in HIV-positive men and women: demographics, utilization patterns and health status. AIDS Care 2001; 13(2): 197–208PubMedCrossRefGoogle Scholar
  41. 41.
    Dausch JG, Nixon DW. Garlic: a review of its relationship to malignant disease. Prev Med 1990; 19(3): 346–61PubMedCrossRefGoogle Scholar
  42. 42.
    Singh UP, Prithiviraj B, Sarma BK, et al. Role of garlic (Allium sativum L.) in human and plant diseases. Indian J Exp Biol 2001; 39(4): 310–22PubMedGoogle Scholar
  43. 43.
    Amagase H, Petesch BL, Matsuura H, et al. Intake of garlic and its bioactive components. J Nutr 2001; 131 Suppl. 3: 955S–62SPubMedGoogle Scholar
  44. 44.
    Markowitz JS, Devane CL, Chavin KD, et al. Effects of garlic (Allium sativum L.) supplementation on cytochrome P450 2D6 and 3A4 activity in healthy volunteers. Clin Pharmacol Ther 2003; 74(2): 170–7PubMedCrossRefGoogle Scholar
  45. 45.
    Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002; 72(3): 276–87PubMedCrossRefGoogle Scholar
  46. 46.
    Fitzsimmons ME, Collins JM. Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome P450 3A4: potential contribution to high first-pass metabolism. Drug Metab Dispos 1997; 25(2): 256–66PubMedGoogle Scholar
  47. 47.
    Foster BC, Foster MS, Vandenhoek S, et al. An in vitro evaluation of human cytochrome P450 3A4 and P-glycoprotein inhibition by garlic. J Pharm Pharm Sci 2001; 4(2): 176–84PubMedGoogle Scholar
  48. 48.
    Piscitelli SC, Burstein AH, Weiden N, et al. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 2002; 34(2): 234–8PubMedCrossRefGoogle Scholar
  49. 49.
    Kim AE, Dintaman JM, Waddell DS. Saquinavir, an HIV protease inhibitor, is transported by P-glycoprotein. J Pharmacol Exp Ther 1998; 286: 143–9Google Scholar
  50. 50.
    Gisolf EH, van Heeswijk RP, Hoetelmans RW, et al. Decreased exposure to saquinavir in HIV-1infected patients after long-term antiretroviral therapy including ritonavir and saquinavir. AIDS 2000; 14: 801–5PubMedCrossRefGoogle Scholar
  51. 51.
    Gallicano K, Foster B, Choudhri S. Effect of short-term administration of garlic supplements on single-dose ritonavir pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2003; 55(2): 199–202PubMedCrossRefGoogle Scholar
  52. 52.
    Hsu A, Granneman GR, Bertz RJ. Ritonavir: clinical pharmacokinetics and interactions with other anti-HIV agents. Clin Pharmacokinet 1998; 35(4): 275–91PubMedCrossRefGoogle Scholar
  53. 53.
    Laroche M, Choudhri S, Gallicano K, et al. Severe gastrointestinal toxicity with concomitant ingestion of ritonavir and garlic [abstract]. Can J Infect Dis 1998; 9 Suppl. A: 471PGoogle Scholar
  54. 54.
    Ernst E. Complementary AIDS therapies: the good, the bad, and the ugly. Int J STD AIDS 1997; 8(5): 281–5PubMedCrossRefGoogle Scholar
  55. 55.
    Sussman E. Garlic supplements can impede HIV medication [letter]. AIDS 2002; 16(9): N5CrossRefGoogle Scholar
  56. 56.
    Sunter WH. Warfarin and garlic [letter]. Pharm J 1991; 246: 772Google Scholar
  57. 57.
    Evans V. Herbs and the brain: friend or foe? The effects of ginkgo and garlic on warfarin use. J Neurosci Nurs 2000; 32(4): 229–32PubMedCrossRefGoogle Scholar
  58. 58.
    German K, Kumar U, Blackford HN. Garlic and the risk of TURP bleeding. Br J Urol 1995; 76(4): 518PubMedCrossRefGoogle Scholar
  59. 59.
    Petry JJ. Garlic and postoperative bleeding. Plast Reconstr Surg 1995; 96(2): 483–4PubMedCrossRefGoogle Scholar
  60. 60.
    Rose KD, Croissant PD, Parliament CF, et al. Spontaneous spinal epidural hematoma with associated platelet dysfunction from excessive garlic ingestion: a case report. Neurosurgery 1990; 26(5): 880–2PubMedCrossRefGoogle Scholar
  61. 61.
    Fedder SL. Spinal epidural hematoma and garlic ingestion [letter]. Neurosurgery 1990; 27(4): 659PubMedCrossRefGoogle Scholar
  62. 62.
    Briggs WH, Xiao H, Parkin KL, et al. Differential inhibition of human platelet aggregation by selected Allium thiosulfinates. J Agric Food Chem 2000; 48(11): 5731–5PubMedCrossRefGoogle Scholar
  63. 63.
    Rahman K, Billington D. Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans. J Nutr 2000; 130(11): 2662–5PubMedGoogle Scholar
  64. 64.
    MacDonald JA, Langler RF. Structure-activity relationships for selected sulfur-rich antithrombotic compounds. Biochem Biophys Res Commun 2000; 273(2): 421–4PubMedCrossRefGoogle Scholar
  65. 65.
    Bordia A, Verma SK, Srivastava KC. Effect of garlic (Allium sativum) on blood lipids, blood sugar, fibrinogen and fibrinolytic activity in patients with coronary artery disease. Prostaglandins Leukot Essent Fatty Acids 1998; 58(4): 257–63PubMedCrossRefGoogle Scholar
  66. 66.
    Aslam M, Stockley IH. Interaction between curry ingredient (karela) and drug (chlorpropamide) [letter]. Lancet 1979; I(8116): 607CrossRefGoogle Scholar
  67. 67.
    Sheela CG, Kumud K, Augusti KT. Anti-diabetic effects of onion and garlic sulfoxide amino acids in rats. Planta Med 1995; 61(4): 356–7PubMedCrossRefGoogle Scholar
  68. 68.
    Sheela CG, Augusti KT. Antidiabetic effects of S-allyl cysteine sulphoxide isolated from garlic Allium sativum Linn. Indian J Exp Biol 1992; 30(6): 523–6PubMedGoogle Scholar
  69. 69.
    Mathew PT, Augusti KT. Studies on the effect of allicin (diallyl disulphide-oxide) on alloxan diabetes. I: hypoglycaemic action and enhancement of serum insulin effect and glycogen synthesis. Indian J Biochem Biophys 1973; 10(3): 209–12PubMedGoogle Scholar
  70. 70.
    Zhang XH, Lowe D, Giles P, et al. Gender may affect the action of garlic oil on plasma cholesterol and glucose levels of normal subjects. J Nutr 2001; 131(5): 1471–8PubMedGoogle Scholar
  71. 71.
    Sitprija S, Plengvidhya C, Kangkaya V, et al. Garlic and diabetes mellitus phase II clinical trial. J Med Assoc Thai 1987; 70 Suppl. 2: 223–7PubMedGoogle Scholar
  72. 72.
    Day C, Cartwright T, Provost J, et al. Hypoglycaemic effect of Momordica charantia extracts. Planta Med 1990; 56(5): 426–9PubMedCrossRefGoogle Scholar
  73. 73.
    Gwilt PR, Lear CL, Tempero MA, et al. The effect of garlic extract on human metabolism of acetaminophen. Cancer Epidemiol Biomarkers Prev 1994; 3(2): 155–60PubMedGoogle Scholar
  74. 74.
    Lin MC, Wang EJ, Patten C, et al. Protective effect of diallyl sulfone against acetaminophen-induced hepatotoxicity in mice. J Biochem Toxicol 1996; 11(1): 11–20PubMedCrossRefGoogle Scholar
  75. 75.
    Manyike PT, Kharasch ED, Kalhorn TF, et al. Contribution of CYP2E1 and CYP3A to acetaminophen reactive metabolite formation. Clin Pharmacol Ther 2000; 67(3): 275–82PubMedCrossRefGoogle Scholar
  76. 76.
    Li H, Dai Y, Zhang H, et al. Pharmacological studies on the Chinese drug radix Angelicae dahuricae. Zhongguo Zhong Yao Za Zhi 1991; 16(9): 560–76PubMedGoogle Scholar
  77. 77.
    Kim CM, Heo MY, Kim HP, et al. Pharmacological activities of water extracts of Umbelliferae plants. Arch Pharm Res 1991; 14(1): 87–92PubMedCrossRefGoogle Scholar
  78. 78.
    Saiki Y, Morinaga K, Okegawa O, et al. On the coumarins of the roots of Angelica dahurica Benth. et Hook. Yakugaku Zasshi 1971; 91(12): 1313–7PubMedGoogle Scholar
  79. 79.
    Baek NI, Ahn EM, Kim HY, et al. Furanocoumarins from the root of Angelica dahurica. Arch Pharm Res 2000; 23(5): 467–70PubMedCrossRefGoogle Scholar
  80. 80.
    Qiao SY, Yao XS, Wang ZY. Coumarins of the roots of Angelica dahurica [abstract]. Planta Med 1996; 62(6): 584PubMedCrossRefGoogle Scholar
  81. 81.
    Ishihara K, Kushida H, Yuzurihara M, et al. Interaction of drugs and Chinese herbs: pharmacokinetic changes of tolbutamide and diazepam caused by extract of Angelica dahurica. J Pharm Pharmacol 2000; 52(8): 1023–9PubMedCrossRefGoogle Scholar
  82. 82.
    Bergendorff O, Dekermendjian K, Nielsen M, et al. Furanocoumarins with affinity to brain benzodiazepine receptors in vitro. Phytochemistry 1997; 44(6): 1121–11124PubMedCrossRefGoogle Scholar
  83. 83.
    Dekermendjian K, Ai JL, Nielsen M, et al. Characterisation of the furanocoumarin phellopterin as a rat brain benzodiazepine receptor partial agonist in vitro. Neurosci Lett 1996; 219(3): 151–4PubMedCrossRefGoogle Scholar
  84. 84.
    Cai Y, Bennett D, Nair RV, et al. Inhibition and inactivation of murine hepatic ethoxy- and pentoxyresorufin O-dealkylase by naturally occurring coumarins. Chem Res Toxicol 1993; 6(6): 872–9PubMedCrossRefGoogle Scholar
  85. 85.
    Kleiner HE, Vulimiri SV, Reed MJ, et al. Role of cytochrome P450 1A1 and 1B1 in the metabolic activation of 7,12-dimethylbenz[a]anthracene and the effects of naturally occurring furanocoumarins on skin tumor initiation. Chem Res Toxicol 2002; 15(2): 226–35PubMedCrossRefGoogle Scholar
  86. 86.
    Kleiner HE, Reed MJ, DiGiovanni J. Naturally occurring coumarins inhibit human cytochromes P450 and block benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene DNA adduct formation in MCF-7 cells. Chem Res Toxicol 2003; 16(3): 415–22PubMedCrossRefGoogle Scholar
  87. 87.
    Maenpaa J, Sigusch H, Raunio H, et al. Differential inhibition of coumarin 7-hydroxylase activity in mouse and human liver microsomes. Biochem Pharmacol 1993; 45(5): 1035–42PubMedCrossRefGoogle Scholar
  88. 88.
    Guo LQ, Taniguchi M, Chen QY, et al. Inhibitory potential of herbal medicines on human cytochrome P450-mediated oxidation: properties of Umbelliferous or Citrus crude drugs and their relative prescriptions. Jpn J Pharmacol 2001; 85(4): 399–408PubMedCrossRefGoogle Scholar
  89. 89.
    Zhu DP. Dong quai. Am J Chin Med 1987; 15(3–4): 117–25PubMedCrossRefGoogle Scholar
  90. 90.
    Lin LZ, He XG, Lian LZ, et al. Liquid Chromatographic electrospray mass spectrometric study of the phthalides of Angelica sinensis and chemical changes of Z-ligustilide. J Chromatogr 1998; 810(1–2): 71–9Google Scholar
  91. 91.
    Zhao KJ, Dong TT, Tu PF, et al. Molecular genetic and chemical assessment of Radix Angelica (Danggui) in China. J Agric Food Chem 2003; 51(9): 2576–83PubMedCrossRefGoogle Scholar
  92. 92.
    Huang WH, Song CQ. Research progresses in the chemistry and pharmacology of Angelica sinensis (Oliv.) Diel [in Chinese]. Zhongguo Zhong Yao Za Zhi 2001; 26(3): 147–51PubMedGoogle Scholar
  93. 93.
    Mao X, Kong L, Luo Q, et al. Screening and analysis of permeable compounds in Radix Angelica Sinensis with immobilized liposome chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 2002; 779(2): 331–9PubMedCrossRefGoogle Scholar
  94. 94.
    Ji SG, Chai YF, Wu YT, et al. Determination of ferulic acid in Angelica sinensis and Chuanxiong by capillary zone electrophoresis. Biomed Chromatogr 1999; 13(5): 333–4PubMedCrossRefGoogle Scholar
  95. 95.
    Guo T, Sun Y, Sui Y, et al. Determination of ferulic acid and adenosine in Angelicae Radix by micellar electrokinetic chromatography. Anal Bioanal Chem 2003; 375(6): 840–3PubMedGoogle Scholar
  96. 96.
    Yang Q, Populo SM, Zhang J, et al. Effect of Angelica sinensis on the proliferation of human bone cells. Clin Chim Acta 2002; 324(1–2): 89–97PubMedCrossRefGoogle Scholar
  97. 97.
    Mei QB, Tao JY, Cui B. Advances in the pharmacological studies of radix Angelica sinensis (Oliv) Diels (Chinese Danggui). Chin Med J (Engl) 1991; 104(9): 776–81Google Scholar
  98. 98.
    Russell L, Hicks GS, Low AK, et al. Phytoestrogens: a viable option? Am J Med Sci 2002; 324(4): 185–8PubMedCrossRefGoogle Scholar
  99. 99.
    He ZP, Wang DZ, Shi LY, et al. Treating amenorrhea in vital energy-deficient patients with angelica sinensis-astragalus membranaceus menstruation-regulating decoction. J Tradit Chin Med 1986; 6(3): 187–90PubMedGoogle Scholar
  100. 100.
    Hardy ML. Herbs of special interest to women. J Am Pharm Assoc (Wash) 2000; 40(2): 234–42Google Scholar
  101. 101.
    Hirata JD, Swiersz LM, Zeil B, et al. Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial. Fertil Steril 1997; 68(6): 981–6PubMedCrossRefGoogle Scholar
  102. 102.
    Page 2nd RL, Lawrence JD. Potentiation of warfarin by dong quai. Pharmacotherapy 1999; 19(7): 870–6PubMedCrossRefGoogle Scholar
  103. 103.
    Yin ZZ, Zhang LY, Xu LN. The effect of Dang-Gui (Angelica sinensis) and its ingredient ferulic acid on rat platelet aggregation and release of 5-HT (author’s transi) [in Chinese]. Yao Xue Xue Bao 1980; 15(6): 321–6PubMedGoogle Scholar
  104. 104.
    Lo ACT, Chan K, Yeung JHK, et al. Danggui (Angelica sinensis) affects the pharmacodynamics but not the pharmacokinetics of warfarin in rabbits. Eur J Drug Metab Pharmacokinet 1995; 20(1): 55–60PubMedCrossRefGoogle Scholar
  105. 105.
    Teel RW, Huynh H. Modulation by phytochemicals of cytochrome P450-linked enzyme activity. Cancer Lett 1998; 133(2): 135–41PubMedCrossRefGoogle Scholar
  106. 106.
    Li T. Siberian ginseng. Horttechnology 2001; 11: 79–84Google Scholar
  107. 107.
    Gaffney B, Hugel H, Rich P. The effects of Eleutherococcus senticosus and Panax ginseng on steroidal hormone indices of stress and lymphocyte subset numbers in endurance athletes. Life Sci 2001; 70(4): 431–42PubMedCrossRefGoogle Scholar
  108. 108.
    Davydov M, Krikorian AD. Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (Araliaceae) as an adaptogen: a closer look. J Ethnopharmacol 2000; 72(3): 345–93PubMedCrossRefGoogle Scholar
  109. 109.
    Hou JP. The chemical constituents of ginseng plants. Comp Med East West 1977; 5(2): 123–45PubMedGoogle Scholar
  110. 110.
    Donovan JL, DeVane CL, Chavin KD, et al. Siberian ginseng (Eleutheroccus senticosus) effects on CYP2D6 and CYP3A4 activity in normal volunteers. Drug Metab Dispos 2003; 31(5): 519–22PubMedCrossRefGoogle Scholar
  111. 111.
    Budzinski JW, Foster BC, Vandenhoek S, et al. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000; 7(4): 273–82PubMedCrossRefGoogle Scholar
  112. 112.
    Medon PJ, Ferguson PW, Watson CF. Effects of Eleuthewcoccus senticosus extracts on hexobarbital metabolism in vivo and in vitro. J Ethnopharmacol 1984; 10(2): 235–41PubMedCrossRefGoogle Scholar
  113. 113.
    Knodell RG, Dubey RK, Wilkinson GR, et al. Oxidative metabolism of hexobarbital in human liver: relationship to polymorphic S-mephenytoin 4-hydroxylation. J Pharmacol Exp Ther 1988; 245(3): 845–9PubMedGoogle Scholar
  114. 114.
    McRae S. Elevated serum digoxin levels in a patient taking digoxin and Siberian ginseng. CMAJ 1996; 155(3): 293–5PubMedGoogle Scholar
  115. 115.
    Dasgupta A, Wu S, Actor J, et al. Effect of Asian and Siberian ginseng on serum digoxin measurement by five digoxin immunoassays: significant variation in digoxin-like immunoreactivity among commercial ginsengs. Am J Clin Pathol 2003; 119(2): 298–303PubMedCrossRefGoogle Scholar
  116. 116.
    Oken BS, Storzbach DM, Kaye JA. The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease. Arch Neurol 1998; 55(11): 1409–15PubMedCrossRefGoogle Scholar
  117. 117.
    McKenna DJ, Jones K, Hughes K. Efficacy, safety, and use of ginkgo biloba in clinical and preclinical applications. Altern Ther Health Med 2001; 7(5): 70–86PubMedGoogle Scholar
  118. 118.
    Wesnes KA, Ward T, McGinty A, et al. The memory enhancing effects of a Ginkgo biloba/Panax ginseng combination in healthy middle-aged volunteers. Psychopharmacology 2000: 152(4): 353–61PubMedCrossRefGoogle Scholar
  119. 119.
    Mahady GB. Ginkgo biloba for the prevention and treatment of cardiovascular disease: a review of the literature}. J Cardiovasc Nurs 2002; 16(4): 21–32PubMedGoogle Scholar
  120. 120.
    Diamond BJ, Shiflett SC, Feiwel N, et al. Ginkgo biloba extract: mechanisms and clinical indications. Arch Phys Med Rehabil 2000; 81(5): 668–78PubMedGoogle Scholar
  121. 121.
    Andrieu S, Gillette S, Amouyal K, et al. Association of Alzheimer’s disease onset with ginkgo biloba and other symptomatic cognitive treatments in a population of women aged 75 years and older from the EPIDOS study. J Gerontol A Biol Sci Med Sci 2003; 58(4): 372–7PubMedCrossRefGoogle Scholar
  122. 122.
    Ponto LL, Schultz SK. Ginkgo biloba extract: review of CNS effects. Ann Clin Psychiatry 2003; 15(2): 109–19PubMedGoogle Scholar
  123. 123.
    Tang YP, Lou FC, Wang JH, et al. Coumaroyl flavonol glycosides from the leaves of Ginkgo biloba. Phytochemistry 2001; 58(8): 1251–6PubMedCrossRefGoogle Scholar
  124. 124.
    Krieglstein J, Ausmeier F, Elabhar H, et al. Neuroprotective effects of Ginkgo biloba constituents. Eur J Pharm Sci 1995; 3(1): 39–48CrossRefGoogle Scholar
  125. 125.
    van Beek TA. Chemical analysis of Ginkgo biloba leaves and extracts. J Chromatogr A 2002; 967(1): 21–55PubMedCrossRefGoogle Scholar
  126. 126.
    Lichtblau D, Berger JM, Nakanishi K. Efficient extraction of ginkgolides and bilobalide from Ginkgo biloba leaves. J Nat Prod 2002; 65(10): 1501–4PubMedCrossRefGoogle Scholar
  127. 127.
    Jaggy H, Koch E. Chemistry and biology of alkylphenols from Ginkgo biloba L. Pharmazie 1997; 52(10): 735–8PubMedGoogle Scholar
  128. 128.
    Baron-Ruppert G, Luepke NP. Evidence for toxic effects of alkylphenols from Ginkgo biloba in the hen’s egg test (HET). Phytomedicine 2001; 8(2): 133–8PubMedCrossRefGoogle Scholar
  129. 129.
    Ahlemeyer B, Selke D, Schaper C, et al. Ginkgolic acids induce neuronal death and activate protein phosphatase type-2C. Eur J Pharmacol 2001; 430(1): 1–7PubMedCrossRefGoogle Scholar
  130. 130.
    Koch E, Jaggy H, Chatterjee SS. Evidence for immunotoxic effects of crude Ginkgo biloba L. leaf extracts using the popliteal lymph node assay in the mouse. Int J Immunopharmacol 2000; 22(3): 229–36PubMedCrossRefGoogle Scholar
  131. 131.
    Lepoittevin JP, Benezra C, Asakawa Y. Allergic contact dermatitis to Ginkgo biloba L.: relationship with urushiol. Arch Dermatol Res 1989; 281(4): 227–30PubMedCrossRefGoogle Scholar
  132. 132.
    Galluzzi S, Zanetti O, Binetti G, et al. Coma in a patient with Alzheimer’s disease taking low dose trazodone and Ginkgo biloba. J Neurol Neurosurg Psychiatry 2000; 68(5): 679–80PubMedCrossRefGoogle Scholar
  133. 133.
    Sasaki K, Hatta S, Haga M, et al. Effects of bilobalide on gamma-aminobutyric acid levels and glutamic acid decarboxylase in mouse brain. Eur J Pharmacol 1999; 367 (2–3): 165–73Google Scholar
  134. 134.
    Sasaki K, Hatta S, Wada K, et al. Bilobalide prevents reduction of gamma-aminobutyric acid levels and glutamic acid decarboxylase activity induced by 4-O-methylpyridoxine in mouse hippocampus. Life Sci 2000; 67(6): 709–15PubMedCrossRefGoogle Scholar
  135. 135.
    Shinozuka K, Umegaki K, Kubota Y, et al. Feeding of Ginkgo biloba extract (GBE) enhances gene expression of hepatic cytochrome P-450 and attenuates the hypotensive effect of nicardipine in rats. Life Sci 2002; 70(23): 2783–92PubMedCrossRefGoogle Scholar
  136. 136.
    Umegaki K, Saito K, Kubota Y, et al. Ginkgo biloba extract markedly induces pentoxyresorufin O-dealkylase activity in rats. Jpn J Pharmacol 2002; 90(4): 345–51PubMedCrossRefGoogle Scholar
  137. 137.
    Sasaki K, Wada K, Hatta S, et al. Bilobalide, a constituent of Ginkgo biloba L., potentiates drug-metabolizing enzyme activities in mice: possible mechanism for anticonvulsant activity against 4-O-methylpyridoxine-induced convulsions. Res Commun Mol Pathol Pharmacol 1997; 96(1): 45–56PubMedGoogle Scholar
  138. 138.
    Vaes LP, Chyka PA. Interactions of warfarin with garlic, ginger, ginkgo, or ginseng: nature of the evidence. Ann Pharmacother 2000; 34(12): 1478–82PubMedCrossRefGoogle Scholar
  139. 139.
    Matthews Jr MK. Association of Ginkgo biloba with intracerebral hemorrhage. Neurology 1998; 50(6): 1933–4PubMedCrossRefGoogle Scholar
  140. 140.
    Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract [letter]. N Engl J Med 1997: 336(15): 1108PubMedCrossRefGoogle Scholar
  141. 141.
    Meisel C, Johne A, Roots I. Fatal intracerebral mass bleeding associated with Ginkgo biloba and ibuprofen. Atherosclerosis 2003; 167(2): 367PubMedCrossRefGoogle Scholar
  142. 142.
    Engelsen J, Nielsen JD, Hansen KF. Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in patients on long-term warfarin treatment: a randomized, double-blind, placebo-controlled cross-over trial [in Danish]. Ugeskr Laeger 2003; 165(18): 1868–71PubMedGoogle Scholar
  143. 143.
    Kim YS, Pyo MK, Park KM, et al. Antiplatelet and antithrombotic effects of a combination of ticlopidine and Ginkgo biloba ext (EGb 761). Thromb Res 1998; 91(1): 33–8PubMedCrossRefGoogle Scholar
  144. 144.
    Lamant V, Mauco G, Braquet P, et al. Inhibition of the metabolism of platelet activating factor (PAF-acether) by three specific antagonists from Ginkgo biloba. Biochem Pharmacol 1987; 36(17): 2749–52PubMedCrossRefGoogle Scholar
  145. 145.
    Fessenden JM, Wittenborn W, Clarke L. Gingko biloba: a case report of herbal medicine and bleeding postoperatively from a laparoscopic cholecystectomy. Am Surg 2001; 67(1): 33–5PubMedGoogle Scholar
  146. 146.
    Skogh M. Extracts of Ginkgo biloba and bleeding or haemorrhage. Lancet 1998; 352(9134): 1145–6PubMedCrossRefGoogle Scholar
  147. 147.
    Vale S. Subarachnoid haemorrhage associated with Ginkgo biloba [letter]. Lancet 1998; 352(9121): 36PubMedCrossRefGoogle Scholar
  148. 148.
    Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. Neurology 1996; 46(6): 1775–6PubMedCrossRefGoogle Scholar
  149. 149.
    Bal Dit Sollier C, Caplain H, Drouet L. No alteration in platelet function or coagulation induced by EGb761 in a controlled study. Clin Lab Haematol 2003; 25(4): 251–3PubMedCrossRefGoogle Scholar
  150. 150.
    Mauro VF, Mauro LS, Kleshinski JF, et al. Impact of ginkgo biloba on the pharmacokinetics of digoxin. Am J Ther 2003; 10(4): 247–51PubMedCrossRefGoogle Scholar
  151. 151.
    Yin OQ, Tomlinson B, Waye MM, et al. Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole. Pharmacogenetics 2004; 14(12): 841–50PubMedCrossRefGoogle Scholar
  152. 152.
    Ohnishi N, Kusuhara M, Yoshioka M, et al. Studies on interactions between functional foods or dietary supplements and medicines. I: effects of Ginkgo biloba leaf extract on the pharmacokinetics of diltiazem in rats. Biol Pharm Bull 2003; 26(9): 1315–20PubMedCrossRefGoogle Scholar
  153. 153.
    Kalus JS, Piotrowski AA, Fortier CR, et al. Hemodynamic and electrocardiographic effects of short-term ginkgo biloba. Ann Pharmacother 2003; 37(3): 345–9PubMedCrossRefGoogle Scholar
  154. 154.
    Mehlsen J, Drabaek H, Wiinberg N, et al. Effects of a Ginkgo biloba extract on forearm haemodynamics in healthy volunteers. Clin Physiol Funct Imaging 2002; 22(6): 375–8PubMedCrossRefGoogle Scholar
  155. 155.
    Jezova D, Duncko R, Lassanova M, et al. Reduction of rise in blood pressure and cortisol release during stress by Ginkgo biloba extract (EGb 761) in healthy volunteers. J Physiol Pharmacol 2002; 53(3): 337–48PubMedGoogle Scholar
  156. 156.
    Kudolo GB. The effect of 3-month ingestion of Ginkgo biloba extract on pancreatic beta-cell function in response to glucose loading in normal glucose tolerant individuals. J Clin Pharmacol 2000; 40(6): 647–54PubMedCrossRefGoogle Scholar
  157. 157.
    Zhang J, Fu S, Liu S, et al. The therapeutic effect of Ginkgo biloba extract in SHR rats and its possible mechanisms based on cerebral microvascular flow and vasomotion. Clin Hemorheol Microcirc 2000; 23(2–4): 133–8PubMedGoogle Scholar
  158. 158.
    Umegaki K, Shinozuka K, Watarai K, et al. Ginkgo biloba extract attenuates the development of hypertension in deoxycorticosterone acetate-salt hypertensive rats. Clin Exp Pharmacol Physiol 2000; 27(4): 277–82PubMedCrossRefGoogle Scholar
  159. 159.
    Chermat R, Brochet D, DeFeudis FV, et al. Interactions of Ginkgo biloba extract (EGb 761), diazepam and ethyl betacarboline-3-carboxylate on social behavior of the rat. Pharmacol Biochem Behav 1997; 56(2): 333–9PubMedCrossRefGoogle Scholar
  160. 160.
    Nordberg A, Svensson AL. Cholinesterase inhibitors in the treatment of Alzheimer’s disease: a comparison of tolerability and pharmacology. Drug Saf 1998; 19(6): 465–80PubMedCrossRefGoogle Scholar
  161. 161.
    Yasui-Furukori N, Furukori H, Kaneda A, et al. The effects of Ginkgo biloba extracts on the pharmacokinetics and pharmacodynamics of donepezil. J Clin Pharmacol 2004; 44(5): 538–42PubMedCrossRefGoogle Scholar
  162. 162.
    Jann MW, Shirley KL, Small GW. Clinical pharmacokinetics and pharmacodynamics of cholinesterase inhibitors. Clin Pharmacokinet 2002; 41(10): 719–39PubMedCrossRefGoogle Scholar
  163. 163.
    Wada K, Ishigaki S, Ueda K, et al. Studies on the constitution of edible and medicinal plants. I: isolation and identification of 4-O-methylpyridoxine, toxic principle from the seed of Ginkgo biloba L. Chem Pharm Bull (Tokyo) 1988; 36(5): 1779–82Google Scholar
  164. 164.
    Scott PM, Lau BP, Lawrence GA, et al. Analysis of Ginkgo biloba for the presence of ginkgotoxin and ginkgotoxin 5’-glucoside. J AOAC Int 2000; 83(6): 1313–20PubMedGoogle Scholar
  165. 165.
    Zhang XY, Zhou DF, Su JM, et al. The effect of extract of Ginkgo biloba added to haloperidol on Superoxide dismutase in inpatients with chronic schizophrenia. J Clin Psychopharmacol 2001; 21(1): 85–8PubMedCrossRefGoogle Scholar
  166. 166.
    Zhang XY, Zhou DF, Zhang PY, et al. A double-blind, placebocontrolled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophrenia. J Clin Psychiatry 2001; 62(11): 878–83PubMedCrossRefGoogle Scholar
  167. 167.
    Kudolo GB. The effect of 3-month ingestion of Ginkgo biloba extract (EGb 761) on pancreatic beta-cell function in response to glucose loading in individuals with non-insulin-dependent diabetes mellitus. J Clin Pharmacol 2001; 41(6): 600–11PubMedCrossRefGoogle Scholar
  168. 168.
    Sugiyama T, Kubota Y, Shinozuka K, et al. Ginkgo biloba extract modifies hypoglycemic action of tolbutamide via hepatic cytochrome P450 mediated mechanism in aged rats. Life Sci 2004; 75(9): 1113–22PubMedCrossRefGoogle Scholar
  169. 169.
    Hatano T, Fukuda T, Miyase T, et al. Phenolic constituents of licorice. III: structures of glicoricone and licofuranone, and inhibitory effects of licorice constituents on monoamine oxidase. Chem Pharm Bull (Tokyo) 1991; 39(5): 1238–43Google Scholar
  170. 170.
    Hatano T, Fukuda T, Liu YZ, et al. Phenolic constituents of licorice. IV: correlation of phenolic constituents and licorice specimens from various sources, and inhibitory effects of licorice extracts on xanthine oxidase and monoamine oxidase. Yakugaku Zasshi 1991; 111(6): 311–21Google Scholar
  171. 171.
    Li C, Homma M, Oka K. Characteristics of delayed excretion of flavonoids in human urine after administration of Shosaiko-to, a herbal medicine. Biol Pharm Bull 1998; 21(12): 1251–7PubMedCrossRefGoogle Scholar
  172. 172.
    Shon JH, Park JY, Kim MS, et al. Effect of licorice (Radix glycyrrhizae) on the pharmacokinetics and pharmacodynamics of midazolam in healthy subjects [abstract]. Clin Pharmacol Ther 2001; 69: P78Google Scholar
  173. 173.
    Gorski JC, Hall SD, Jones DR, et al. Regioselective biotransformation of midazolam by members of the human cytochrome P450 3A (CYP3A) subfamily. Biochem Pharmacol 1994; 47(9): 1643–53PubMedCrossRefGoogle Scholar
  174. 174.
    Kent UM, Aviram M, Rosenblat M, et al. The licorice root derived isoflavan glabridin inhibits the activities of human cytochrome P450S 3A4, 2B6, and 2C9. Drug Metab Dispos 2002; 30(6): 709–15PubMedCrossRefGoogle Scholar
  175. 175.
    Paolini M, Pozzetti L, Sapone A, et al. Effect of licorice and glycyrrhizin on murine liver CYP-dependent monooxygenases. Life Sci 1998; 62(6): 571–82PubMedCrossRefGoogle Scholar
  176. 176.
    Homma M, Oka K, Ikeshima K, et al. Different effects of traditional Chinese medicines containing similar herbal constituents on prednisolone pharmacokinetics. J Pharm Pharmacol 1995; 47(8): 687–92PubMedCrossRefGoogle Scholar
  177. 177.
    Akao T, Terasawa T, Hiai S, et al. Inhibitory effects of glycyrrhetic acid derivatives on 11 beta- and 3 alpha-hydroxysteroid dehydrogenases of rat liver. Chem Pharm Bull (Tokyo) 1992; 40(11): 3021–4CrossRefGoogle Scholar
  178. 178.
    Ojima M, Satoh K, Gomibuchi T, et al. The inhibitory effects of glycyrrhizin and glycyrrhetinic acid on the metabolism of cortisol and prednisolone: in vivo and in vitro studies. Nippon Naibunpi Gakkai Zasshi 1990; 66(5): 584–96PubMedGoogle Scholar
  179. 179.
    Davis EA, Morris DJ. Medicinal uses of licorice through the millennia: the good and plenty of it. Mol Cell Endocrinol 1991; 78(1–2): 1–6PubMedCrossRefGoogle Scholar
  180. 180.
    Teelucksingh S, Mackie AD, Burt D, et al. Potentiation of hydrocortisone activity in skin by glycyrrhetinic acid. Lancet 1990; 335(8697): 1060–3PubMedCrossRefGoogle Scholar
  181. 181.
    Souness GW, Morris DJ. The antinatriuretic and kaliuretic effects of the glucocorticoids corticosterone and cortisol following pretreatment with carbenoxolone sodium (a liquorice derivative) in the adrenalectomized rat. Endocrinology 1989; 124(3): 1588–90PubMedCrossRefGoogle Scholar
  182. 182.
    Elinav E, Chajek-Shaul T. Licorice consumption causing severe hypokalemic paralysis. Mayo Clin Proc 2003; 78(6): 767–8PubMedCrossRefGoogle Scholar
  183. 183.
    Lin SH, Yang SS, Chau T, et al. An unusual cause of hypokalemic paralysis: chronic licorice ingestion. Am J Med Sci 2003; 325(3): 153–6PubMedCrossRefGoogle Scholar
  184. 184.
    Nishimura N, Naora K, Hirano H, et al. Effects of sho-saiko-to (xiao chai hu tang), a Chinese traditional medicine, on the gastric function and absorption of tolbutamide in rats. Yakugaku Zasshi 2001; 121(2): 153–9PubMedCrossRefGoogle Scholar
  185. 185.
    Nishimura N, Naora K, Hirano H, et al. Effects of Sho-saiko-to on the pharmacokinetics and pharmacodynamics of tolbutamide in rats. J Pharm Pharmacol 1998; 50(2): 231–6PubMedCrossRefGoogle Scholar
  186. 186.
    Bilia AR, Gallori S, Vincieri FF. St John’s wort and depression: efficacy, safety and tolerability: an update. Life Sci 2002; 70(26): 3077–96PubMedCrossRefGoogle Scholar
  187. 187.
    Obach RS. Inhibition of human cytochrome P450 enzymes by constituents of St John’s wort, an herbal preparation used in the treatment of depression. J Pharmacol Exp Ther 2000; 294(1): 88–95PubMedGoogle Scholar
  188. 188.
    Erdelmeier CAJ. Hyperforin, possibly the major non-nitrogenous secondary metabolite of Hypericum perforatum L. Pharmacopsychiatry 1998; 31S: 2–6CrossRefGoogle Scholar
  189. 189.
    Moore LB, Goodwin B, Jones SA, et al. St John’s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci U S A 2000; 97(13): 7500–2PubMedCrossRefGoogle Scholar
  190. 190.
    Kerb R, Brockmoller J, Staffeldt B, et al. Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin. Antimicrob Agents Chemother 1996; 40(9): 2087–93PubMedGoogle Scholar
  191. 191.
    Schulz HU, Schurer M, Bassler D, et al. Investigation of the bioavailability of hypericin, pseudohypericin, hyperforin and the flavonoids quercetin and isorhamnetin following single and multiple oral dosing of a hypericum extract containing tablet. Arzneimittelforschung 2005; 55(1): 15–22PubMedGoogle Scholar
  192. 192.
    Johne A, Schmider J, Brockmoller J, et al. Decreased plasma levels of amitriptyline and its metabolites on comedication with an extract from St John’s wort (Hypericum perforatum). J Clin Psychopharmacol 2002; 22(1): 46–54PubMedCrossRefGoogle Scholar
  193. 193.
    Venkatakrishnan K, Schmider J, Harmatz JS, et al. Relative contribution of CYP3A to amitriptyline clearance in humans: in vitro and in vivo studies. J Clin Pharmacol 2001; 41(10): 1043–54PubMedCrossRefGoogle Scholar
  194. 194.
    Venkatakrishnan K, Greenblatt DJ, von Moltke LL, et al. Five distinct human cytochromes mediate amitriptyline N-demethylation in vitro: dominance of CYP 2C19 and 3A4. J Clin Pharmacol 1998; 38(2): 112–21PubMedGoogle Scholar
  195. 195.
    Venkatakrishnan K, von Moltke LL, Greenblatt DJ. Nortriptyline E-10-hydroxylation in vitro is mediated by human CYP2D6 (high affinity) and CYP3A4 (low affinity): implications for interactions with enzyme-inducing drugs. J Clin Pharmacol 1999; 39(6): 567–77PubMedCrossRefGoogle Scholar
  196. 196.
    von Moltke LL, Greenblatt DJ, Harmatz JS, et al. Triazolam biotransformation by human liver microsomes in vitro: effects of metabolic inhibitors and clinical confirmation of a predicted interaction with ketoconazole. J Pharmacol Exp Ther 1996; 276(2): 370–9Google Scholar
  197. 197.
    Markowitz JS, DeVane CL, Boulton DW, et al. Effect of St John’s wort (Hypericum perforatum) on cytochrome P-450 2D6 and 3A4 activity in healthy volunteers. Life Sci 2000; 66(9): PL133–9PubMedCrossRefGoogle Scholar
  198. 198.
    Wang ZQ, Gorski C, Hamman MA, et al. The effects of St John’s wort (Hypericum perforatum) on human cytochrome P450 activity. Clin Pharmacol Ther 2001; 70(4): 317–26PubMedGoogle Scholar
  199. 199.
    Dresser GK, Schwarz UI, Wilkinson GR, et al. Coordinate induction of both cytochrome P4503A and MDR1 by St John’s wort in healthy subjects. Clin Pharmacol Ther 2003; 73(1): 41–50PubMedCrossRefGoogle Scholar
  200. 200.
    Burstein AH, Horton RL, Dunn T, et al. Lack of effect of St John’s wort on carbamazepine pharmacokinetics in healthy volunteers. Clin Pharmacol Ther 2000; 68(6): 605–12PubMedCrossRefGoogle Scholar
  201. 201.
    Pelkonen O, Myllynen P, Taavitsainen P, et al. Carbamazepine: a ‘blind’ assessment of CYP-associated metabolism and interactions in human liver-derived in vitro systems. Xenobiotica 2001; 31(6): 321–43PubMedCrossRefGoogle Scholar
  202. 202.
    Kerr BM, Thummel KE, Wurden CJ, et al. Human liver carbamazepine metabolism: Role of CYP3A4 and CYP2C8 in 10, 11-epoxide formation. Biochem Pharmacol 1994; 47(11): 1969–79PubMedCrossRefGoogle Scholar
  203. 203.
    Tateishi T, Asoh M, Nakura H, et al. Carbamazepine induces multiple cytochrome P450 subfamilies in rats. Chem Biol Interact 1999; 117(3): 257–68PubMedCrossRefGoogle Scholar
  204. 204.
    Kudriakova TB, Sirota LA, Rozova GI, et al. Autoinduction and steady-state pharmacokinetics of carbamazepine and its major metabolites. Br J Clin Pharmacol 1992; 33(6): 611–5PubMedCrossRefGoogle Scholar
  205. 205.
    Owen A, Pirmohamed M, Tettey JN, et al. Carbamazepine is not a substrate for P-glycoprotein. Br J Clin Pharmacol 2001; 51(4): 345–9PubMedCrossRefGoogle Scholar
  206. 206.
    Ohnishi N, Nakasako S, Okada K, et al. Studies on interactions between traditional herbal and western medicines. IV: lack of pharmacokinetic interactions between Saiko-ka-ryukotsuborei-to and carbamazepine in rats. Eur J Drug Metab Pharmacokinet 2001; 26(1–2): 129–35PubMedCrossRefGoogle Scholar
  207. 207.
    Akhlaghi F, Trull AK. Distribution of cyclosporin in organ transplant recipients. Clin Pharmacokinet 2002; 41(9): 615–37PubMedCrossRefGoogle Scholar
  208. 208.
    Lown KS, Mayo RR, Leichtman AB, et al. Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine. Clin Pharm Ther 1997; 62(3): 248–60CrossRefGoogle Scholar
  209. 209.
    Christians U, Strohmeyer S, Kownatzki R, et al. Investigations on the metabolic pathways of cyclosporine. II: elucidation of the metabolic pathways in vitro by human liver microsomes. Xenobiotica 1991; 21(9): 1199–210Google Scholar
  210. 210.
    Kronbach T, Fischer V, Meyer UA. Cyclosporine metabolism in human liver: identification of a cytochrome P-450III gene family as the major cyclosporine-metabolizing enzyme explains interactions of cyclosporine with other drugs. Clin Pharmacol Ther 1988; 43(6): 630–5PubMedCrossRefGoogle Scholar
  211. 211.
    Combalbert J, Fabre I, Fabre G, et al. Metabolism of cyclosporin A. IV: purification and identification of the rifampicin-inducible human liver cytochrome P-450 (cyclosporin A oxidase) as a product of P450IIIA gene subfamily. Drug Metab Dispos 1989; 17(2): 197–207Google Scholar
  212. 212.
    Jurima-Romet M, Crawford K, Cyr T, et al. Terfenadine metabolism in human liver: in vitro inhibition by macrolide antibiotics and azole antifungals. Drug Metab Dispos 1994; 22(6): 849–57PubMedGoogle Scholar
  213. 213.
    Fahr A. Cyclosporin clinical pharmacokinetics. Clin Pharmacokinet 1993; 24: 472–95PubMedCrossRefGoogle Scholar
  214. 214.
    Christians U, Strohmeyer S, Kownatzki R, et al. Investigations on the metabolic pathways of cyclosporine: I. Excretion of cyclosporine and its metabolites in human bile: isolation of 12 new cyclosporine metabolites. Xenobiotica 1991; 21(9): 1185–98Google Scholar
  215. 215.
    Maurer G, Lemaire M. Biotransformation and distribution in blood of cyclosporine and its metabolites. Transplant Proc 1986; 18: 25–34PubMedGoogle Scholar
  216. 216.
    Ruschitzka F, Meier PJ, Turina M, et al. Acute heart transplant rejection due to Saint John’s wort. Lancet 2000; 355(9203): 548–9PubMedCrossRefGoogle Scholar
  217. 217.
    Barone GW, Gurley BJ, Ketel BL, et al. Drug interaction between St John’s wort and cyclosporine. Ann Pharmacother 2000; 34(9): 1013–6PubMedCrossRefGoogle Scholar
  218. 218.
    Mai I, Kruger H, Budde K, et al. Hazardous pharmacokinetic interaction of Saint John’s wort (Hypericum perforatum) with the immunosuppressant cyclosporin. Int J Clin Pharmacol Ther 2000; 38(10): 500–2PubMedGoogle Scholar
  219. 219.
    Karliova M, Treichel U, Malago M, et al. Interaction of Hypericum perforatum (St John’s wort) with cyclosporin A metabolism in a patient after liver transplantation. J Hepatol 2000; 33(5): 853–5PubMedCrossRefGoogle Scholar
  220. 220.
    Breidenbach T, Kliem V, Burg M, et al. Profound drop of cyclosporin A whole blood trough levels caused by St John’s wort (Hypericum perforatum). Transplantation 2000; 69(10): 2229–30PubMedCrossRefGoogle Scholar
  221. 221.
    Bauer S, Stornier E, Johne A, et al. Alterations in cyclosporin A pharmacokinetics and metabolism during treatment with St John’s wort in renal transplant patients. Br J Clin Pharmacol 2003; 55(2): 203–11PubMedCrossRefGoogle Scholar
  222. 222.
    Wieling J, Tamminga WJ, Sakiman EP, et al. Evaluation of analytical and clinical performance of a dual-probe phenotyping method for CYP2D6 polymorphism and CYP3A4 activity screening. Ther Drug Monit 2000; 22(4): 486–96PubMedCrossRefGoogle Scholar
  223. 223.
    Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics 2002; 3(2): 229–43PubMedCrossRefGoogle Scholar
  224. 224.
    Johne A, Brockmoller J, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John’s wort (Hypericum perforatum). Clin Pharmacol Ther 1999; 66(4): 338–45PubMedCrossRefGoogle Scholar
  225. 225.
    Lacarelle B, Rahmani R, de Sousa G, et al. Metabolism of digoxin, digoxigenin digitoxosides and digoxigenin in human hepatocytes and liver microsomes. Fundam Clin Pharmacol 1991; 5(7): 567–82PubMedCrossRefGoogle Scholar
  226. 226.
    Salphati L, Benet LZ. Metabolism of digoxin and digoxigenin digitoxosides in rat liver microsomes: involvement of cytochrome P4503A. Xenobiotica 1999; 29(2): 171–85PubMedCrossRefGoogle Scholar
  227. 227.
    Durr D, Stieger B, Kullak-Ublick GA, et al. St John’s wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 2000; 68: 598–604PubMedCrossRefGoogle Scholar
  228. 228.
    Schinkel AH, Wagenaar E, van Deemter L, et al. Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J Clin Invest 1995; 96(4): 1698–705PubMedCrossRefGoogle Scholar
  229. 229.
    Drescher S, Glaeser H, Murdter T, et al. P-glycoprotein-mediated intestinal and biliary digoxin transport in humans. Clin Pharmacol Ther 2003; 73(3): 223–31PubMedCrossRefGoogle Scholar
  230. 230.
    Gault H, Longerich L, Dawe M, et al. Digoxin-rifampin interaction. Clin Pharmacol Ther 1984; 35(6): 750–4PubMedCrossRefGoogle Scholar
  231. 231.
    Rameis H. On the interaction between phenytoin and digoxin. Eur J Clin Pharmacol 1985; 29(1): 49–53PubMedCrossRefGoogle Scholar
  232. 232.
    Conseil G, Baubichon-Cortay H, Dayan G, et al. Flavonoids: a class of modulators with bifunctional interactions at vicinal ATP: and steroid-binding sites on mouse P-glycoprotein. Proc Natl Acad Sci U S A 1998; 95(17): 9831–6PubMedCrossRefGoogle Scholar
  233. 233.
    Markham A, Wagstaff AJ. Fexofenadine. Drugs 1998; 55(2): 269–74PubMedCrossRefGoogle Scholar
  234. 234.
    Cvetkovic M, Leake B, Fromm MF, et al. OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos 1999; 27(8): 866–71PubMedGoogle Scholar
  235. 235.
    Tian R, Koyabu N, Takanaga H, et al. Effects of grapefruit juice and orange juice on the intestinal efflux of P-glycoprotein substrates. Pharm Res 2002; 19(6): 802–9PubMedCrossRefGoogle Scholar
  236. 236.
    Lippert C, Ling J, Brown P, et al. Mass balance and pharmacokinetics of MDL 16455A in healthy male volunteers [abstract]. Pharm Res 1995; 12: S390Google Scholar
  237. 237.
    Woosley RL, Chen Y, Freiman JP, et al. Mechanism of the cardiotoxic actions of terfenadine. JAMA 1993; 269: 1532–6PubMedCrossRefGoogle Scholar
  238. 238.
    Wang ZQ, Hamman MA, Huang SM, et al. Effect of St John’s wort on the pharmacokinetics of fexofenadine. Clin Pharmacol Ther 2002; 71(6): 414–20PubMedCrossRefGoogle Scholar
  239. 239.
    Johnson JR, Bross P, Cohen M, et al. Approval summary: imatinib mesylate capsules for treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase. Clin Cancer Res 2003; 9(6): 1972–9PubMedGoogle Scholar
  240. 240.
    Cohen MH, Williams G, Johnson JR, et al. Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia. Clin Cancer Res 2002; 8(5): 935–42PubMedGoogle Scholar
  241. 241.
    Cohen MH, Johnson JR, Pazdur R. U.S. Food and Drug Administration Drug Approval Summary: conversion of imatinib mesylate (STI571; Gleevec) tablets from accelerated approval to full approval. Clin Cancer Res 2005; 11(1): 12–9Google Scholar
  242. 242.
    Frye RF, Fitzgerald SM, Lagattuta TF, et al. Effect of St John’s wort on imatinib mesylate pharmacokinetics. Clin Pharmacol Ther 2004; 76(4): 323–9PubMedCrossRefGoogle Scholar
  243. 243.
    Smith P. The influence of St. John’s wort on the pharmacokinetics and protein binding of imatinib mesylate. Pharmacotherapy 2004; 24(11): 1508–14Google Scholar
  244. 244.
    Bolton AE, Peng B, Hubert M, et al. Effect of rifampicin on the pharmacokinetics of imatinib mesylate (Gleevec, STI571) in healthy subjects. Cancer Chemother Pharmacol 2004; 53(2): 102–6PubMedCrossRefGoogle Scholar
  245. 245.
    Mathijssen RH, Verweij J, de Bruijn P, et al. Effects of St John’s wort on irinotecan metabolism. J Natl Cancer Inst 2002; 94(16): 1247–9PubMedCrossRefGoogle Scholar
  246. 246.
    Eich-Hochli D, Oppliger R, Golay KP, et al. Methadone maintenance treatment and St John’s wort: a case report. Pharmacopsychiatry 2003; 36(1): 35–7PubMedCrossRefGoogle Scholar
  247. 247.
    Moody DE, Alburges ME, Parker RJ, et al. The involvement of cytochrome P450 3A4 in the N-demethylation of L-alpha-acetylmethadol (LAAM), norLAAM, and methadone. Drug Metab Dispos 1997; 25(12): 1347–53PubMedGoogle Scholar
  248. 248.
    Wang JS, De Vane CL. Involvement of CYP3A4, CYP2C8, and CYP2D6 in the metabolism of (R)- and (S)-methadone in vitro. Drug Metab Dispos 2003; 31(6): 742–7PubMedCrossRefGoogle Scholar
  249. 249.
    Borgelt-Hansen L. Oral contraceptives: an update on health benefits and risks. J Am Pharm Assoc (Wash) 2001; 41(6): 875–86Google Scholar
  250. 250.
    Burkman RT, Collins JA, Shulman LP, et al. Current perspectives on oral contraceptive use. Am J Obstet Gynecol 2001; 185 (2 Suppl.): S4–12PubMedCrossRefGoogle Scholar
  251. 251.
    Thummel KE, Wilkinson GR. In vitro and in vivo drug interactions involving human CYP3A. Annu Rev Pharmacol Toxicol 1998; 38: 389–430PubMedCrossRefGoogle Scholar
  252. 252.
    Guengerich FP. Oxidation of 17-ethynylestradiol by human liver cytochrome P450. Mol Pharmacol 1988; 33(5): 500–8PubMedGoogle Scholar
  253. 253.
    Murphy PA. St John’s wort and oral contraceptives: reasons for concern? J Midwifery Womens Health 2002; 47(6): 447–50PubMedCrossRefGoogle Scholar
  254. 254.
    Shader RI, Greenblatt DJ. More on oral contraceptives, drug interactions, herbal medicines, and hormone replacement therapy. J Clin Psychopharmacol 2000; 20(4): 397–8PubMedCrossRefGoogle Scholar
  255. 255.
    Ernst E. Second thoughts about safety of St John’s wort. Lancet 1999; 354(9195): 2014–6PubMedCrossRefGoogle Scholar
  256. 256.
    Bolt HM. Interactions between clinically used drugs and oral contraceptives. Environ Health Perspect 1994; 102 Suppl. 9: 35–8PubMedCrossRefGoogle Scholar
  257. 257.
    Yue QY, Bergquist C, Gerden B. Safety of St John’s wort (Hypericum perforatum). Lancet 2000; 355: 548–9CrossRefGoogle Scholar
  258. 258.
    Schwarz UI, Buschel B, Kirch W. Unwanted pregnancy on self-medication with St John’s wort despite hormonal contraception. Br J Clin Pharmacol 2003; 55(2): 112–3PubMedGoogle Scholar
  259. 259.
    Kaufeler R, Meier B, Brattstrom A. Ze 117: clinical efficacy and safety [abstract]. In: Roots I, Kemper FH, editors. Abstract book symposium on Phytopharmaka VII. Research and clinical applications. Berlin: Symposium Organising Committee, 2001 Oct 12–13Google Scholar
  260. 260.
    Piscitelli SC, Burstein AH, Chaitt D, et al. Indinavir concentrations and St John’s wort. Lancet 2000; 355(9203): 547–8PubMedCrossRefGoogle Scholar
  261. 261.
    Chiba M, Hensleigh M, Nishime JA, et al. Role of cytochrome P450 in human metabolism of MK-639, a potent human immunodeficiency virus protease inhibitor. Drug Metab Dispos 1996; 24: 307–14PubMedGoogle Scholar
  262. 262.
    Decker CJ, Laitinen LM, Bridson GW, et al. Metabolism of amprenavir in liver microsomes: role of CYP3A4 inhibition for drug interactions. J Pharm Sci 1998; 87(7): 803–7PubMedCrossRefGoogle Scholar
  263. 263.
    de Maat MM, Hoetelmans RM, Mathot RA, et al. Drug interaction between St John’s wort and nevirapine. AIDS 2001; 15(3): 420–1PubMedCrossRefGoogle Scholar
  264. 264.
    Erickson DA, Mather G, Trager WF, et al. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P-450. Drug Metab Dispos 1999; 27(12): 1488–95PubMedGoogle Scholar
  265. 265.
    Kawaguchi A, Ohmori M, Tsuruoka S, et al. Drug interaction between St John’s Wort and quazepam. Br J Clin Pharmacol 2004; 58(4): 403–10PubMedCrossRefGoogle Scholar
  266. 266.
    Vaswani M, Linda FK, Ramesh S. Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27(1): 85–102PubMedCrossRefGoogle Scholar
  267. 267.
    Lantz MS, Buchalter E, Giambanco V. St John’s wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatry Neurol 1999; 12(1): 7–10PubMedCrossRefGoogle Scholar
  268. 268.
    Gordon JB. SSRIs and St John’s wort: possible toxicity? Am Fam Physician 1998; 57(5): 950–3PubMedGoogle Scholar
  269. 269.
    Barbenel DM, Yusufi B, O’Shea D, et al. Mania in a patient receiving testosterone replacement postorchidectomy taking St John’s wort and sertraline. J Psychopharmacol 2000; 14(1): 84–6PubMedCrossRefGoogle Scholar
  270. 270.
    Spinella M, Eaton LA. Hypomania induced by herbal and pharmaceutical psychotropic medicines following mild traumatic brain injury. Brain Inj 2002; 16(4): 359–67PubMedCrossRefGoogle Scholar
  271. 271.
    Dannawi M. Possible serotonin syndrome after combination of buspirone and St John’s wort [letter]. J Psychopharmacol 2002; 16(4): 401PubMedCrossRefGoogle Scholar
  272. 272.
    Cookson J. Side-effects of antidepressants. Br J Psychiatry 1993; 163 Suppl. 20: 20–4Google Scholar
  273. 273.
    Roz N, Mazur Y, Hirshfeld A, et al. Inhibition of vesicular uptake of monoamines by hyperforin. Life Sci 2002; 71(19): 2227–37PubMedCrossRefGoogle Scholar
  274. 274.
    Wonnemann M, Singer A, Siebert B, et al. Evaluation of synaptosomal uptake inhibition of most relevant constituents of St John’s wort. Pharmacopsychiatry 2001; 34 Suppl. 1: S148–51PubMedCrossRefGoogle Scholar
  275. 275.
    Butterweck V, Bockers T, Korte B, et al. Long-term effects of St John’s wort and hypericin on monoamine levels in rat hypothalamus and hippocampus. Brain Res 2002; 930(1–2): 21–9PubMedCrossRefGoogle Scholar
  276. 276.
    Nathan PJ. Hypericum perforatum (St John’s wort): a non-selective reuptake inhibitor? A review of the recent advances in its pharmacology. J Psychopharmacol 2001; 15(1): 47–54PubMedCrossRefGoogle Scholar
  277. 277.
    Parker V, Wong AH, Boon HS, et al. Adverse reactions to St John’s wort. Can J Psychiatry 2001; 46(1): 77–9PubMedGoogle Scholar
  278. 278.
    Beckman SE, Sommi RW, Switzer J. Consumer use of St John’s wort: a survey on effectiveness, safety, and tolerability. Pharmacotherapy 2000; 20(5): 568–74PubMedCrossRefGoogle Scholar
  279. 279.
    Sugimoto K, Ohmori M, Tsuruoka S, et al. Different effects of St John’s Wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther 2001; 70(6): 518–24PubMedCrossRefGoogle Scholar
  280. 280.
    Bolley R, Zulke C, Kammerl M, et al. Tacrolimus-induced nephrotoxicity unmasked by induction of the CYP3A4 system with St John’s wort [letter]. Transplantation 2002; 73(6): 1009PubMedCrossRefGoogle Scholar
  281. 281.
    Mai I, Stornier E, Bauer S, et al. Impact of St John’s wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients. Nephrol Dial Transplant 2003; 18(4): 819–22PubMedCrossRefGoogle Scholar
  282. 282.
    Nebel A, Schneider BJ, Baker RK, et al. Potential metabolic interaction between St John’s wort and theophylline [letter]. Ann Pharmacother 1999; 33(4): 502PubMedCrossRefGoogle Scholar
  283. 283.
    Sarkar MA, Hunt C, Guzelian PS, et al. Characterization of human liver cytochromes P-450 involved in theophylline metabolism. Drug Metab Dispos 1992; 20(1): 31–7PubMedGoogle Scholar
  284. 284.
    Maurer A, Johne A, Bauer S. Interaction of St John’s wort extract with phenprocoumon [abstract]. Eur J Clin Pharmacol 1999; 55: A22Google Scholar
  285. 285.
    He M, Korzekwa KR, Jones JP, et al. Structural forms of phenprocoumon and warfarin that are metabolized at the active site of CYP2C9. Arch Biochem Biophys 1999; 372(1): 16–28PubMedCrossRefGoogle Scholar
  286. 286.
    Kaminsky LS, Zhang ZY. Human P450 metabolism of warfarin. Pharmacol Ther 1997; 73(1): 67–74PubMedCrossRefGoogle Scholar
  287. 287.
    Goodwin B, Moore LB, Stoltz CM, et al. Regulation of the human CYP2B6 gene by the nuclear pregnane X receptor. Mol Pharmacol 2001; 60(3): 427–31PubMedGoogle Scholar
  288. 288.
    Wentworth JM, Agostini M, Love J, et al. St John’s wort, a herbal antidepressant, activates the steroid X receptor. J Endocrinol 2000; 166(3): R11–6PubMedCrossRefGoogle Scholar
  289. 289.
    Bray BJ, Perry NB, Menkes DB, et al. St John’s wort extract induces CYP3A and CYP2E1 in the Swiss Webster mouse. Toxicol Sci 2002; 66(1): 27–33PubMedCrossRefGoogle Scholar
  290. 290.
    Roby CA, Anderson GD, Kantor E, et al. St John’s wort: effect on CYP3A4 activity. Clin Pharmacol Ther 2000; 67(5): 451–7PubMedCrossRefGoogle Scholar
  291. 291.
    Hennessy M, Kelleher D, Spiers JP, et al. St John’s wort increases expression of P-glycoprotein: implications for drug interactions. Br J Clin Pharmacol 2002; 53(1): 75–82PubMedCrossRefGoogle Scholar
  292. 292.
    Perloff MD, von Moltke LL, Stornier E, et al. Saint John’s wort: an in vitro analysis of P-glycoprotein induction due to extended exposure. Br J Pharmacol 2001; 134(8): 1601–8PubMedCrossRefGoogle Scholar
  293. 293.
    Xie R, Tan LH, Polasek EC, et al. CYP3A and P-glycoprotein activity induction with St. John’s wort in healthy volunteers from 6 ethnic populations. J Clin Pharmacol 2005; 45(3): 352–6Google Scholar
  294. 294.
    Moschella C, Jaber BL. Interaction between cyclosporine and Hypericum perforatum (St John’s wort) after organ transplantation. Am J Kidney Dis 2001; 38(5): 1105–7PubMedCrossRefGoogle Scholar
  295. 295.
    Kane GC, Lipsky JJ. Drug-grapefruit juice interactions. Mayo Clin Proc 2000; 75(9): 933–42PubMedCrossRefGoogle Scholar
  296. 296.
    Bailey DG, Malcolm J, Arnold O, et al. Grapefruit juice-drug interactions. Br J Clin Pharmacol 1998; 46(2): 101–10PubMedCrossRefGoogle Scholar
  297. 297.
    Hunter J, Hirst BH. Intestinal secretion of drugs: the role of p-glycoprotein and related drug efflux systems in limiting oral drug absorption. Adv Drug Deliver Rev 1997; 25: 129–57CrossRefGoogle Scholar
  298. 298.
    Zhang YC, Benet LZ. The gut as a barrier to drug absorption: combined role of cytochrome P450 3A and P-glycoprotein. Clin Pharmacokinet 2001; 40(3): 159–68PubMedCrossRefGoogle Scholar
  299. 299.
    Wang MQ, Guilbert LJ, Ling L, et al. Immunomodulating activity of CVT-E002, a proprietary extract from North American ginseng (Panax quinquefolium). J Pharm Pharmacol 2001; 53(11): 1515–23PubMedCrossRefGoogle Scholar
  300. 300.
    Liao BS, Newmark H, Zhou RP. Neuroprotective effects of ginseng total saponin and ginsenosides Rb1 and Rg1 on spinal cord neurons in vitro. Exp Neurol 2002; 173(2): 224–34PubMedCrossRefGoogle Scholar
  301. 301.
    Deyama T, Nishibe S, Nakazawa Y. Constituents and pharmacological effects of Eucommia and Siberian ginseng. Acta Pharmacol Sin 2001; 22(12): 1057–70PubMedGoogle Scholar
  302. 302.
    Chi JG. Cancer chemoprevention of INSAM (Ginseng): foreword [abstract]. J Korean Med Sci 2001; 16 Suppl. S: S1Google Scholar
  303. 303.
    Nishino H, Tokuda H, Li T, et al. Cancer chemoprevention by ginseng in mouse liver and other organs. J Korean Med Sci 2001; 16 Suppl. S: S66–9PubMedGoogle Scholar
  304. 304.
    Han BH, Han YN, Park MH, et al. Chemistry and biochemistry of ginseng components: ginsenosides and antioxidants. In: Mori A, Satoh A, editors. Emerging drugs: molecular aspects of Asian medicines. Singapore: World Scientific Publisher, 2001: 387–98Google Scholar
  305. 305.
    Kitagawa I, Yoshikawa M, Yoshihara M, et al. Chemical studies of crude drugs (1): constituents of Ginseng radix rubra [in Japanese]. Yakugaku Zasshi 1983; 103: 612–22PubMedGoogle Scholar
  306. 306.
    Bae EA, Han MJ, Choo MK, et al. Metabolism of 20 (S)- and 20 (R)-ginsenoside R-g3 by human intestinal bacteria and its relation to in vitro biological activities. Biol Pharm Bull 2002; 25(1): 58–63PubMedCrossRefGoogle Scholar
  307. 307.
    Coon JT, Ernst E. Panax ginseng: a systematic review of adverse effects and drug interactions. Drug Saf 2002; 25(5): 323–44PubMedCrossRefGoogle Scholar
  308. 308.
    Lee FC, Ko JH, Park JK, et al. Effects of Panax ginseng on blood alcohol clearance in man. Clin Exp Pharmacol Physiol 1987; 14(6): 543–6PubMedCrossRefGoogle Scholar
  309. 309.
    Agarwal DP. Genetic polymorphisms of alcohol metabolizing enzymes. Pathol Biol (Paris) 2001; 49(9): 703–9CrossRefGoogle Scholar
  310. 310.
    Ashmarin IP, Danilova RA, Obukhova MF, et al. Main ethanol metabolizing alcohol dehydrogenases (ADH I and ADH IV): biochemical functions and the physiological manifestation. FEBS Lett 2000; 486(1): 49–51PubMedCrossRefGoogle Scholar
  311. 311.
    Koo MW. Effects of ginseng on ethanol induced sedation in mice. Life Sci 1999; 64(2): 153–60PubMedCrossRefGoogle Scholar
  312. 312.
    Petkov V, Koushev V, Panova Y. Accelerated ethanol elimination under the effect of Ginseng (experiments on rats). Acta Physiol Pharmacol Bulg 1977; 3(1): 46–50PubMedGoogle Scholar
  313. 313.
    Lee YJ, Pantuck CB, Pantuck EJ. Effect of ginseng on plasma levels of ethanol in the rat. Planta Med 1993; 59(1): 17–9PubMedCrossRefGoogle Scholar
  314. 314.
    Shader RI, Greenblatt DJ. Phenelzine and the dream machine: ramblings and reflections. J Clin Psychopharmacol 1985; 5(2): 65PubMedCrossRefGoogle Scholar
  315. 315.
    Jones BD, Runikis AM. Interaction of ginseng with phenelzine. J Clin Psychopharmacol 1987; 7(3): 201–2PubMedCrossRefGoogle Scholar
  316. 316.
    Shader RI, Greenblatt DJ. Bees, ginseng and MAOIs revisited. J Clin Psychopharmacol 1988; 8(4): 235PubMedCrossRefGoogle Scholar
  317. 317.
    Sala F, Mulet J, Choi S, et al. Effects of ginsenoside Rg2 on human neuronal nicotinic acetylcholine receptors. J Pharmacol Exp Ther 2002; 301(3): 1052–9PubMedCrossRefGoogle Scholar
  318. 318.
    Toda N, Ayajiki K, Fujioka H, et al. Ginsenoside potentiates NO-mediated neurogenic vasodilatation of monkey cerebral arteries. J Ethnopharmacol 2001; 76(1): 109–13PubMedCrossRefGoogle Scholar
  319. 319.
    Liu D, Li B, Liu Y, et al. Voltage-dependent inhibition of brain Na (+) channels by American ginseng. Eur J Pharmacol 2001: 413(1): 47–54PubMedCrossRefGoogle Scholar
  320. 320.
    Kim S, Ahn K, Oh TH, et al. Inhibitory effect of ginsenosides on NMDA receptor-mediated signals in rat hippocampal neurons. Biochem Biophys Res Commun 2002; 296(2): 247–54PubMedCrossRefGoogle Scholar
  321. 321.
    Baker GB, Urichuk LJ, McKenna KF, et al. Metabolism of monoamine oxidase inhibitors. Cell Mol Neurobiol 1999; 19(3): 411–26PubMedCrossRefGoogle Scholar
  322. 322.
    Janetzky K, Morreale AP. Probable interaction between warfarin and ginseng. Am J Health Syst Pharm 1997; 54(6): 692–3PubMedGoogle Scholar
  323. 323.
    Jiang X, Williams KM, Liauw WS, et al. Effect of St John’s wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2004; 57(5): 592–9PubMedCrossRefGoogle Scholar
  324. 324.
    Yuan CS, Wei G, Dey L, et al. Brief communication: American ginseng reduces warfarin’s effect in healthy patients: a randomized, controlled trial. Ann Intern Med 2004; 141(1): 23–7PubMedGoogle Scholar
  325. 325.
    Cui X, Sakaguchi T, Shirai Y, et al. Orally administered Panax ginseng extract decreases platelet adhesiveness in 66% hepatectomized rats. Am J Chin Med 1999; 27(2): 251–6PubMedCrossRefGoogle Scholar
  326. 326.
    Yun YP, Do JH, Ko SR, et al. Effects of Korean red ginseng and its mixed prescription on the high molecular weight dextraninduced blood stasis in rats and human platelet aggregation. J Ethnopharmacol 2001; 77(2–3): 259–64PubMedCrossRefGoogle Scholar
  327. 327.
    Jung KY, Kim DS, Oh SR, et al. Platelet activating factor antagonist activity of ginsenosides. Biol Pharm Bull 1998; 21(1): 79–80PubMedCrossRefGoogle Scholar
  328. 328.
    Kuo SC, Teng CM, Lee JC, et al. Antiplatelet components in Panax ginseng. Planta Med 1990; 56(2): 164–7PubMedCrossRefGoogle Scholar
  329. 329.
    Zhu M, Chan KW, Ng LS, et al. Possible influences of ginseng on the pharmacokinetics and pharmacodynamics of warfarin in rats. J Pharm Pharmacol 1999; 51(2): 175–80PubMedCrossRefGoogle Scholar
  330. 330.
    Nguyen TD, Villard PH, Barlatier A, et al. Panax vietnamensis protects mice against carbon tetrachloride-induced hepatotoxicity without any modification of CYP2E1 gene expression. Planta Med 2000; 66(8): 714–9PubMedCrossRefGoogle Scholar
  331. 331.
    Chang TKH, Chen J, Benetton SA. In vitro effect of standardized ginseng extracts and individual ginsenosides on the catalytic activity of human CYP1A1, CYP1A2, and CYP1B1. Drug Metab Dispos 2002; 30(4): 378–84PubMedCrossRefGoogle Scholar
  332. 332.
    Henderson GL, Harkey MR, Gershwin ME, et al. Effects of ginseng components on c-DNA-expressed cytochrome P450 enzyme catalytic activity. Life Sci 1999; 65(15): PL209–14PubMedCrossRefGoogle Scholar
  333. 333.
    Furutsu M, Koyama Y, Kusakabe M, et al. Preventive effect of the extract of Du-zhong (Tochu) leaf and ginseng root on acute toxicity of chlorpyrifos. Jpn J Toxicol Environ Health 1997; 43(2): 92–100CrossRefGoogle Scholar
  334. 334.
    Kim HJ, Chun YJ, Park JD, et al. Protection of rat liver micro-somes against carbon tetrachloride-induced lipid peroxidation by red ginseng saponin through cytochrome P450 inhibition. Planta Med 1997; 63(5): 415–8PubMedCrossRefGoogle Scholar
  335. 335.
    Scaglione F, Cattaneo G, Alessandria M, et al. Efficacy and safety of the standardised Ginseng extract G115 for potentiating vaccination against the influenza syndrome and protection against the common cold [corrected; published erratum appears in Drugs Exp Clin Res 1996; 22 (6): 338]}. Drugs Exp Clin Res 1996; 22(2): 65–72PubMedGoogle Scholar
  336. 336.
    Rivera E, Hu S, Concha C. Ginseng and aluminium hydroxide act synergistically as vaccine adjuvants. Vaccine 2003; 21(11–12): 1149–57PubMedCrossRefGoogle Scholar
  337. 337.
    Hu S, Concha C, Lin F, et al. Adjuvant effect of ginseng extracts on the immune responses to immunisation against Staphylococcus aureus in dairy cattle. Vet Immunol Immunopathol 2003; 91(1): 29–37PubMedCrossRefGoogle Scholar
  338. 338.
    Rivera E, Daggfeldt A, Hu S. Ginseng extract in aluminium hydroxide adjuvanted vaccines improves the antibody response of pigs to porcine parvovirus and Erysipelothrix rhusiopathiae. Vet Immunol Immunopathol 2003; 91(1): 19–27PubMedCrossRefGoogle Scholar
  339. 339.
    Singh YN, Singh NN. Therapeutic potential of kava in the treatment of anxiety disorders. CNS Drugs 2002; 16(11): 731–43PubMedCrossRefGoogle Scholar
  340. 340.
    Volz HP, Kieser M. Kava-kava extract WS 1490 versus placebo in anxiety disorders: a randomized placebo-controlled 25-week outpatient trial. Pharmacopsychiatry 1997; 30(1): 1–5PubMedCrossRefGoogle Scholar
  341. 341.
    Pittler MH, Ernst E. Efficacy of kava extract for treating anxiety: systematic review and meta-analysis. J Clin Psychopharmacol 2000; 20(2): 84–9PubMedCrossRefGoogle Scholar
  342. 342.
    Rouse J. Kava: a South Pacific herb for anxiety, tension and insomnia. Clin Nutr Insights 1998; 96: 3900–5Google Scholar
  343. 343.
    Wheatley D. Stress-induced insomnia treated with kava and valerian: singly and in combination. Hum Psychopharmacol 2001; 16(4): 353–6PubMedCrossRefGoogle Scholar
  344. 344.
    Stevinson C, Huntley A, Ernst E. A systematic review of the safety of kava extract in the treatment of anxiety. Drug Saf 2002; 25(4): 251–61PubMedCrossRefGoogle Scholar
  345. 345.
    Bilia AR, Gallon S, Vincieri FF. Kava-kava and anxiety: growing knowledge about the efficacy and safety. Life Sci 2002; 70(22): 2581–97PubMedCrossRefGoogle Scholar
  346. 346.
    Lebot V, Lévesque J. The origin and distribution of kava (Piper methysticum Forst, f. and Piper wichmannii C. DC, Piperaceae): a phytochemical approach. Allertonia 1989; 5: 223–80Google Scholar
  347. 347.
    Zou L, Harkey MR, Henderson GL. Effects of herbal components on cDNA-expressed cytochrome P450 enzyme catalytic activity. Life Sci 2002; 71(13): 1579–89PubMedCrossRefGoogle Scholar
  348. 348.
    Anke J, Ramzan I. Pharmacokinetic and pharmacodynamic drug interactions with Kava (Piper methysticum Forst, f.) J Ethnopharmacol 2004; 93(2–3): 153–60PubMedCrossRefGoogle Scholar
  349. 349.
    Herberg KW. Effect of Kava-Special Extract WS 1490 combined with ethyl alcohol on safety-relevant performance parameters [in German]. Blutalkohol 1993; 30(2): 96–105PubMedGoogle Scholar
  350. 350.
    Jamieson DD, Duffield PH. Positive interaction of ethanol and kava resin in mice. Clin Exp Pharmacol Physiol 1990; 17(7): 509–14PubMedCrossRefGoogle Scholar
  351. 351.
    Almeida JC, Grimsley EW. Coma from the health food store: interaction between Kava and alprazolam. Ann Intern Med 1996; 125(11): 940–1PubMedGoogle Scholar
  352. 352.
    Yuan CS, Dey L, Wang A, et al. Kavalactones and dihydrokavain modulate GABAergic activity in a rat gastric-brainstem preparation. Planta Med 2002; 68(12): 1092–6PubMedCrossRefGoogle Scholar
  353. 353.
    Jussofie A, Schmiz A, Hiemke C. Kavapyrone enriched extract from Piper methysticum as modulator of the GABA binding site in different regions of rat brain. Psychopharmacology (Berl) 1994; 116(4): 469–74PubMedCrossRefGoogle Scholar
  354. 354.
    Gorski JC, Jones DR, Hamman MA, et al. Biotransformation of alprazolam by members of the human cytochrome P4503A subfamily. Xenobiotica 1999; 29(9): 931–44PubMedCrossRefGoogle Scholar
  355. 355.
    Herberg KW. Safety-related performance after intake of kava-extract, bromazepam and their combination. Z Allgemeinmed 1996; 72: 973–7Google Scholar
  356. 356.
    Schelosky L, Raffauf C, Jendroska K, et al. Kava and dopamine antagonism. J Neurol Neurosurg Psychiatry 1995; 58(5): 639–40PubMedCrossRefGoogle Scholar
  357. 357.
    Baum SS, Hill R, Rommelspacher H. Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats. Prog Neuropsychopharmacol Biol Psychiatry 1998; 22(7): 1105–20PubMedCrossRefGoogle Scholar
  358. 358.
    Meseguer E, Taboada R, Sanchez V, et al. Life-threatening parkinsonism induced by kava-kava. Mov Disord 2002; 17(1): 195–6PubMedCrossRefGoogle Scholar
  359. 359.
    Bajad S, Bedi KL, Singla AK, et al. Piperine inhibits gastric emptying and gastrointestinal transit in rats and mice. Planta Med 2001; 67(2): 176–9PubMedCrossRefGoogle Scholar
  360. 360.
    Hiwale AR, Dhuley JN, Naik SR. Effect of co-administration of piperine on pharmacokinetics of beta-lactam antibiotics in rats. Indian J Exp Biol 2002; 40(3): 277–81PubMedGoogle Scholar
  361. 361.
    Gupta SK, Bansal P, Bhardwaj RK, et al. Comparative anti-nociceptive, anti-inflammatory and toxicity profile of nimesulide vs nimesulide and piperine combination. Pharm Res 2000; 41(6): 657–62CrossRefGoogle Scholar
  362. 362.
    Mujumdar AM, Dhuley JN, Deshmukh VK, et al. Effect of piperine on pentobarbitone induced hypnosis in rats. Indian J Exp Biol 1990; 28(5): 486–7PubMedGoogle Scholar
  363. 363.
    Shoba G, Joy D, Joseph T, et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998; 64(4): 353–6PubMedCrossRefGoogle Scholar
  364. 364.
    Badmaev VV, Majeed M, Prakash L. Piperine derived from black pepper increases the plasma levels of coenzyme q10 following oral supplementation. J Nutr Biochem 2000; 11(2): 109–13PubMedCrossRefGoogle Scholar
  365. 365.
    Bano G, Raina RK, Zutshi U, et al. Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. Eur J Clin Pharmacol 1991; 41(6): 615–7PubMedCrossRefGoogle Scholar
  366. 366.
    Johnson JA, Herring VL, Wolfe MS, et al. CYP1A2 and CYP2D6 4-hydroxylate propranolol and both reactions exhibit racial differences. J Pharmacol Exp Ther 2000; 294(3): 1099–105PubMedGoogle Scholar
  367. 367.
    Ching MS, Bichara N, Blake CL, et al. Propranolol 4- and 5-hydroxylation and N-desisopropylation by cloned human cytochrome P4501A1 and P4501A2. Drug Metab Dispos 1996; 24(6): 692–4PubMedGoogle Scholar
  368. 368.
    Yoshimoto K, Echizen H, Chiba K, et al. Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers: N-desisopropylation is mediated mainly by CYP1A2. Br J Clin Pharmacol 1995; 39(4): 421–31PubMedCrossRefGoogle Scholar
  369. 369.
    Singh J, Reen RK. Modulation of constitutive, benz[a]anthracene- and phenobarbital-inducible cytochromes-P450 activities in rat hepatoma H4IIEC3/G-cells by piperine. Curr Sci 1994; 66(5): 365–9Google Scholar
  370. 370.
    Dalvi RR, Dalvi PS. Comparison of the effects of piperine administered intragastrically and intraperitoneally on the liver and liver mixed-function oxidases in rats. Drug Metabol Drug Interact 1991; 9(1): 23–30PubMedCrossRefGoogle Scholar
  371. 371.
    Kang MH, Won SM, Park SS, et al. Piperine effects on the expression of P4502E1, P4502B and P4501A in rat. Xenobiotica 1994; 24(12): 1195–204PubMedCrossRefGoogle Scholar
  372. 372.
    Zutshi RK, Singh R, Zutshi U, et al. Influence of piperine on rifampicin blood levels in patients of pulmonary tuberculosis. J Assoc Physicians India 1985; 33: 223–4PubMedGoogle Scholar
  373. 373.
    Schuetz EG, Schinkel AH, Relling MV, et al. P-glycoprotein: a major determinant of rifampicin-inducible expression of cytochrome P4503A in mice and humans. Proc Natl Acad Sci U S A 1996; 93: 4001–5PubMedCrossRefGoogle Scholar
  374. 374.
    Bhardwaj RK, Glaeser H, Becquemont L, et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002; 302(2): 645–50PubMedCrossRefGoogle Scholar
  375. 375.
    Atal CK, Zutshi U, Rao PG. Scientific evidence on the role of Ayurvedic herbals on bioavailability of drugs. J Ethnopharmacol 1981; 4: 229–32PubMedCrossRefGoogle Scholar
  376. 376.
    Dalvi RR, Dalvi PS. Differences in the effects of piperine and piperonyl butoxide on hepatic drug-metabolizing enzyme system in rats. Drug Chem Toxicol 1991; 14(1–2): 219–29PubMedCrossRefGoogle Scholar
  377. 377.
    Tjia JF, Colbert J, Back DJ. Theophylline metabolism in human liver microsomes: inhibition studies. J Pharmacol Exp Ther 1996; 276(3): 912–7PubMedGoogle Scholar
  378. 378.
    Ha HR, Chen J, Freiburghaus AU, et al. Metabolism of theophylline by cDNA-expressed human cytochromes P-450. Br J Clin Pharmacol 1995; 39(3): 321–6PubMedCrossRefGoogle Scholar
  379. 379.
    Velpandian T, Jasuja R, Bhardwaj RK, et al. Piperine in food: interference in the pharmacokinetics of phenytoin. Eur J Drug Metab Pharmacokinet 2001; 26(4): 241–7PubMedCrossRefGoogle Scholar
  380. 380.
    Bano G, Amla V, Raina RK, et al. The effect of piperine on pharmacokinetics of phenytoin in healthy volunteers. Planta Med 1987; 53(6): 568–9PubMedCrossRefGoogle Scholar
  381. 381.
    Tsukamoto S, Cha BC, Ohta T. Dipiperamides A, B, and C: bisalkaloids from the white pepper Piper nigrum inhibiting CYP3A4 activity. Tetrahedron 2002; 58(9): 1667–71CrossRefGoogle Scholar
  382. 382.
    Veronese ME, Mackenzie PI, Doecke CJ, et al. Tolbutamide and phenytoin hydroxylations by cDNA-expressed human liver cytochrome P4502C9. Biochem Biophys Res Commun 1991; 175(3): 1112–8PubMedCrossRefGoogle Scholar
  383. 383.
    Bajpai M, Roskos LK, Shen DD, et al. Roles of cytochrome P4502C9 and cytochrome P4502C19 in the stereoselective metabolism of phenytoin to its major metabolite. Drug Metab Dispos 1996; 24(12): 1401–14PubMedGoogle Scholar
  384. 384.
    Cuttle L, Munns AJ, Hogg NA, et al. Phenytoin metabolism by human cytochrome P450: involvement of P450 3A and 2C forms in secondary metabolism and drug-protein adduct formation. Drug Metab Dispos 2000; 28(8): 945–50PubMedGoogle Scholar
  385. 385.
    Munns AJ, De Voss JJ, Hooper WD, et al. Bioactivation of phenytoin by human cytochrome P450: characterization of the mechanism and targets of covalent adduct formation. Chem Res Toxicol 1997; 10(9): 1049–58PubMedCrossRefGoogle Scholar
  386. 386.
    Komatsu T, Yamazaki H, Asahi S, et al. Formation of a dihydroxy metabolite of phenytoin in human liver microsomes/cytosol: roles of cytochromes P4502C9, 2C19, and 3A4. Drug Metab Dispos 2000; 28(11): 1361–8PubMedGoogle Scholar
  387. 387.
    Schinkel AH, Wagenaar E, Mol CA, et al. P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J Clin Invest 1996; 97: 2517–24PubMedCrossRefGoogle Scholar
  388. 388.
    Cummins CL, Jacobsen W, Benet LZ. Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002; 300(3): 1036–45PubMedCrossRefGoogle Scholar
  389. 389.
    Ji XY, Tan BK, Zhu YZ. Salvia miltiorrhiza and ischemic diseases. Acta Pharmacol Sin 2000; 21(12): 1089–94PubMedGoogle Scholar
  390. 390.
    Lee AR, Wu WL, Chang WL, et al. Isolation and bioactivity of new tanshinones. J Nat Prod 1987; 50(2): 157–60PubMedCrossRefGoogle Scholar
  391. 391.
    Chan TY. Interaction between warfarin and danshen (Salvia miltiorrhiza). Ann Pharmacother 2001; 35(4): 501–4PubMedCrossRefGoogle Scholar
  392. 392.
    Yu CM, Chan JC, Sanderson JE. Chinese herbs and warfarin potentiation by ‘danshen’. J Intern Med 1997; 241(4): 337–9PubMedCrossRefGoogle Scholar
  393. 393.
    Au-Yeung KK, Zhu DY, O K, et al. Inhibition of stress-activated protein kinase in the ischemic/reperfused heart: role of magnesium tanshinoate B in preventing apoptosis. Biochem Pharmacol 2001; 62(4): 483–93PubMedCrossRefGoogle Scholar
  394. 394.
    Zhou W, Ruigrok TJ. Protective effect of danshen during myocardial ischemia and reperfusion: an isolated rat heart study. Am J Chin Med 1990; 18(1–2): 19–24PubMedCrossRefGoogle Scholar
  395. 395.
    Wu TW, Zeng LH, Fung KP, et al. Effect of sodium tanshinone IIA sulfonate in the rabbit myocardium and on human cardiomyocytes and vascular endothelial cells. Biochem Pharmacol 1993; 46(12): 2327–32PubMedCrossRefGoogle Scholar
  396. 396.
    Kim SY, Moon TC, Chang HW, et al. Effects of tanshinone I isolated from Salvia miltiorrhiza bunge on arachidonic acid metabolism and in vivo inflammatory responses. Phytother Res 2002; 16(7): 616–20PubMedCrossRefGoogle Scholar
  397. 397.
    Oh SH, Nan JX, Sohn DW, et al. Salvia miltiorrhiza inhibits biliary obstruction-induced hepatocyte apoptosis by cytoplasmic sequestration of p53. Toxicol Appl Pharmacol 2002; 182(1): 27–33PubMedCrossRefGoogle Scholar
  398. 398.
    Lee TY, Mai LM, Wang GJ, et al. Protective mechanism of Salvia miltiorrhiza on carbon tetrachloride-induced acute hepatotoxicity in rats. J Pharmacol Sci 2003; 91(3): 202–10PubMedCrossRefGoogle Scholar
  399. 399.
    Peng Y, Liu F, Luo J, et al. Effects of danshen and shengmaiye on glomerulosclerosis by adriamycin in rats [in Chinese]. Hunan Yi Ke Da Xue Xue Bao 1999; 24(4): 332–4PubMedGoogle Scholar
  400. 400.
    Sato M, Sato T, Ose Y, et al. Modulating effect of tanshinones on mutagenic activity of Trp-P-1 and benzo[a]pyrene in Salmonella typhimurium. Mutat Res 1992; 265(2): 149–54PubMedCrossRefGoogle Scholar
  401. 401.
    Abd-Elazem IS, Chen HS, Bates RB, et al. Isolation of two highly potent and non-toxic inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase from Salvia miltiorrhiza. Antiviral Res 2002; 55(1): 91–106PubMedCrossRefGoogle Scholar
  402. 402.
    Kang BY, Chung SW, Kim SH, et al. Inhibition of interleukin-12 and interferon-gamma production in immune cells by tanshinones from Salvia miltiorrhiza. Immunopharmacology 2000; 49(3): 355–61PubMedCrossRefGoogle Scholar
  403. 403.
    Ryu SY, Oak MH, Kim KM. Inhibition of mast cell degranulation by tanshinones from the roots of Salvia miltiorrhiza. Planta Med 1999; 65(7): 654–5PubMedCrossRefGoogle Scholar
  404. 404.
    O K, Lynn EG, Vazhappilly R, et al. Magnesium tanshinoate B (MTB) inhibits low density lipoprotein oxidation. Life Sci 2001; 68(8): 903–12PubMedCrossRefGoogle Scholar
  405. 405.
    Zhao BL, Jiang W, Zhao Y, et al. Scavenging effects of salvia miltiorrhiza on free radicals and its protection for myocardial mitochondrial membranes from ischemia-reperfusion injury. Biochem Mol Biol Int 1996; 38(6): 1171–82PubMedGoogle Scholar
  406. 406.
    Kang DG, Yun YG, Ryoo JH, et al. Anti-hypertensive effect of water extract of danshen on renovascular hypertension through inhibition of the renin angiotensin system. Am J Chin Med 2002; 30(1): 87–93PubMedCrossRefGoogle Scholar
  407. 407.
    Wang GZ, Ru X, Ding LH, et al. Short term effect of Salvia miltiorrhiza in treating rat acetic acid chronic gastric ulcer and long term effect in preventing recurrence. World J Gastroenterol 1998; 4(2): 169–70PubMedGoogle Scholar
  408. 408.
    Lay IS, Chiu JH, Shiao MS, et al. Crude extract of Salvia miltiorrhiza and salvianolic acid B enhance in vitro angiogenesis in murine SVR endothelial cell line. Planta Med 2003; 69(1): 26–32PubMedCrossRefGoogle Scholar
  409. 409.
    Liu J, Shen HM, Ong CN. Role of intracellular thiol depletion, mitochondrial dysfunction and reactive oxygen species in Salvia miltiorrhiza-induced apoptosis in human hepatoma HepG2 cells. Life Sci 2001; 69(16): 1833–50PubMedCrossRefGoogle Scholar
  410. 410.
    Wu WL, Chang WL, Chen CF. Cytotoxic activities of tanshinones against human carcinoma cell lines. Am J Chin Med 1991; 19(3–4): 207–16PubMedCrossRefGoogle Scholar
  411. 411.
    Izzat MB, Yim APC, El-Zufari MH. A taste of Chinese medicine! Ann Thorac Surg 1998; 66: 941–942PubMedCrossRefGoogle Scholar
  412. 412.
    Cheng TO. Warfarin danshen interaction [letter]. Ann Thorac Surg 1999; 67(3): 894PubMedGoogle Scholar
  413. 413.
    Lo AC, Chan K, Yeung JH, et al. The effects of danshen (Salvia miltiorrhiza) on pharmacokinetics and pharmacodynamics of warfarin in rats. Eur J Drug Metab Pharmacokinet 1992; 17(4): 257–62PubMedCrossRefGoogle Scholar
  414. 414.
    Petitpas I, Bhattacharya AA, Twine S, et al. Crystal structure analysis of warfarin binding to human serum albumin: anatomy of drug site I. J Biol Chem 2001; 276(25): 22804–9PubMedCrossRefGoogle Scholar
  415. 415.
    Fitos I, Visy J, Kardos J. Stereoselective kinetics of warfarin binding to human serum albumin: effect of an allosteric interaction. Chirality 2002; 14(5): 442–8PubMedCrossRefGoogle Scholar
  416. 416.
    Gupta D, Jalali M, Wells A, et al. Drug-herb interactions: unexpected suppression of free Danshen concentrations by salicylate. J Clin Lab Anal 2002; 16(6): 290–4PubMedCrossRefGoogle Scholar
  417. 417.
    Makino T, Wakushima H, Okamoto T, et al. Pharmacokinetic interactions between warfarin and kangen-karyu, a Chinese traditional herbal medicine, and their synergistic action. J Ethnopharmacol 2002; 82(1): 35–40PubMedCrossRefGoogle Scholar
  418. 418.
    Tang W, Eisenbrand G. Scutellaria baicalensis Georgi: Chinese drugs of plant original. Heidelberg: Springer-Verlag, 1992CrossRefGoogle Scholar
  419. 419.
    Qi L, Zhou R, Wang YF, et al. Study of major flavonoids in crude Scutellariae Radix by micellar electrokinetic capillary chromatography. J Capillary Electrophor 1998; 5(5–6): 181–4PubMedGoogle Scholar
  420. 420.
    Taniguchi C, Homma M, Takano O, et al. Pharmacological effects of urinary products obtained after treatment with saiboku-to, a herbal medicine for bronchial asthma, on type IV allergic reaction. Planta Med 2000; 66(7): 607–11PubMedCrossRefGoogle Scholar
  421. 421.
    Hou YN, Zhu XY, Cheng GF. Effects of baicalin on liver microsomal cytochrome P450 system [in Chinese]. Yao Xue Xue Bao 2000; 35(12): 890–2PubMedGoogle Scholar
  422. 422.
    Lin CC, Shieh DE. The anti-inflammatory activity of Scutellaria rivularis extracts and its active components, baicalin, baicalein and wogonin. Am J Chin Med 1996; 24(1): 31–6PubMedCrossRefGoogle Scholar
  423. 423.
    Shieh DE, Liu LT, Lin CC. Antioxidant and free radical scavenging effects of baicalein, baicalin and wogonin. Anticancer Res 2000; 20(5A): 2861–5PubMedGoogle Scholar
  424. 424.
    Gao Z, Huang K, Yang X, et al. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim Biophys Acta 1999; 1472(3): 643–50PubMedCrossRefGoogle Scholar
  425. 425.
    Ikemoto S, Sugimura K, Yoshida N, et al. Antitumor effects of Scutellariae radix and its components baicalein, baicalin, and wogonin on bladder cancer cell lines. Urology 2000; 55(6): 951–5PubMedCrossRefGoogle Scholar
  426. 426.
    Akao T, Kawabata K, Yanagisawa E, et al. Baicalin, the predominant flavone glucuronide of scutellariae radix, is absorbed from the rat gastrointestinal tract as the aglycone and restored to its original form. J Pharm Pharmacol 2000; 52(12): 1563–8PubMedCrossRefGoogle Scholar
  427. 427.
    Wakui Y, Yanagisawa E, Ishibashi E, et al. Determination of baicalin and baicalein in rat plasma by high-performance liquid chromatography with electrochemical detection. J Chromatogr 1992; 575(1): 131–6PubMedCrossRefGoogle Scholar
  428. 428.
    Lai MY, Hsiu SL, Tsai SY, et al. Comparison of metabolic pharmacokinetics of baicalin and baicalein in rats. J Pharm Pharmacol 2003; 55(2): 205–9PubMedCrossRefGoogle Scholar
  429. 429.
    Lai MY, Hsiu SL, Chen CC, et al. Urinary pharmacokinetics of baicalein, wogonin and their glycosides after oral administration of Scutellariae Radix in humans. Biol Pharm Bull 2003; 26(1): 79–83PubMedCrossRefGoogle Scholar
  430. 430.
    Canal P, Gay C, Dezeuze A, et al. Pharmacokinetics and pharmacodynamics of irinotecan during a phase II clinical trial in colorectal cancer: Pharmacology and Molecular Mechanisms Group of the European Organization for Research and Treatment of Cancer. J Clin Oncol 1996; 14(10): 2688–95PubMedGoogle Scholar
  431. 431.
    Gupta E, Mick R, Ramirez J, et al. Pharmacokinetic and pharmacodynamic evaluation of the topoisomerase inhibitor irinotecan in cancer patients. J Clin Oncol 1997; 15(4): 1502–10PubMedGoogle Scholar
  432. 432.
    Kudoh S, Fujiwara Y, Takada Y, et al. Phase II study of irinotecan combined with cisplatin in patients with previously untreated small-cell lung cancer. West Japan Lung Cancer Group. J Clin Oncol 1998; 16(3): 1068–74Google Scholar
  433. 433.
    Humerickhouse R, Lohrbach K, Li L, et al. Characterization of CPT-11 hydrolysis by human liver carboxylesterase isoforms hCE-1 and hCE-2. Cancer Res 2000; 60(5): 1189–92PubMedGoogle Scholar
  434. 434.
    Bencharit S, Morton CL, Howard-Williams EL, et al. Structural insights into CPT-11 activation by mammalian carboxylesterases. Nat Struct Biol 2002; 9(5): 337–42PubMedCrossRefGoogle Scholar
  435. 435.
    Rivory LP, Bowles MR, Robert J, et al. Conversion of irinotecan (CPT-11) to its active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN-38), by human liver carboxylesterase. Biochem Pharmacol 1996; 52(7): 1103–11PubMedCrossRefGoogle Scholar
  436. 436.
    Hanioka N, Ozawa S, Jinno H, et al. Human liver UDP-glucuronosyltransferase isoforms involved in the glucuronidation of 7-ethyl-10-hydroxycamptothecin. Xenobiotica 2001; 31(10): 687–99PubMedCrossRefGoogle Scholar
  437. 437.
    Mathijssen RHJ, van Alphen RJ, Verweij J, et al. Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin Cancer Res 2001; 7(8): 2182–94PubMedGoogle Scholar
  438. 438.
    Santos A, Zanetta S, Cresteil T, et al. Metabolism of irinotecan (CPT-11) by CYP3A4 and CYP3A5 in humans. Clin Cancer Res 2000; 6(5): 2012–20PubMedGoogle Scholar
  439. 439.
    Sugiyama Y, Kato Y, Chu X. Multiplicity of biliary excretion mechanisms for the camptothecin derivative irinotecan (CPT-11), its metabolite SN-38, and its glucuronide: role of canalicular multispecific organic anion transporter and P-glycoprotein. Cancer Chemother Pharmacol 1998; 42 Suppl.: S44–9PubMedCrossRefGoogle Scholar
  440. 440.
    Gupta E, Lestingi TM, Mick R, et al. Metabolic fate of irinotecan in humans: correlation of glucuronidation with diarrhea. Cancer Res 1994; 54(14): 3723–5PubMedGoogle Scholar
  441. 441.
    Xie R, Mathijssen RH, Sparreboom A, et al. Clinical pharmacokinetics of irinotecan and its metabolites in relation with diarrhea. Clin Pharmacol Ther 2002; 72(3): 265–75PubMedCrossRefGoogle Scholar
  442. 442.
    Mori K, Kondo T, Kamiyama Y, et al. Preventive effect of Kampo medicine (Hangeshashin-to) against irinotecan-induced diarrhea in advanced non-small-cell lung cancer. Cancer Chemother Pharmacol 2003; 51(5): 403–6PubMedGoogle Scholar
  443. 443.
    Takasuna K, Kasai Y, Kitano Y, et al. Protective effects of kampo medicines and baicalin against intestinal toxicity of a new anticancer camptothecin derivative, irinotecan hydrochloride (CPT-11), in rats. Jpn J Cancer Res 1995; 86(10): 978–84PubMedCrossRefGoogle Scholar
  444. 444.
    Kase Y, Hayakawa T, Aburada M, et al. Preventive effects of Hange-shashin-to on irinotecan hydrochloride-caused diarrhea and its relevance to the colonic prostaglandin E2 and water absorption in the rat. Jpn J Pharmacol 1997; 75(4): 407–13PubMedCrossRefGoogle Scholar
  445. 445.
    Kase Y, Hayakawa T, Togashi Y, et al. Relevance of irinotecan hydrochloride-induced diarrhea to the level of prostaglandin E2 and water absorption of large intestine in rats. Jpn J Pharmacol 1997; 75(4): 399–405PubMedCrossRefGoogle Scholar
  446. 446.
    Narita M, Nagai E, Hagiwara H, et al. Inhibition of betaglucuronidase by natural glucuronides of kampo medicines using glucuronide of SN-38 (7-ethyl-10-hydroxy-camptothecin) as a substrate. Xenobiotica 1993; 23(1): 5–10PubMedCrossRefGoogle Scholar
  447. 447.
    Chu XY, Suzuki H, Ueda K, et al. Active efflux of CPT-11 and its metabolites in human KB-derived cell lines. J Pharmacol Exp Ther 1999; 288(2): 735–41PubMedGoogle Scholar
  448. 448.
    Chu XY, Kato Y, Ueda K, et al. Biliary excretion mechanism of CPT-11 and its metabolites in humans: involvement of primary active transporters. Cancer Res 1998; 58(22): 5137–43PubMedGoogle Scholar
  449. 449.
    Chu XY, Kato Y, Niinuma K, et al. Multispecific organic anion transporter is responsible for the biliary excretion of the camptothecin derivative irinotecan and its metabolites in rats. J Pharmacol Exp Ther 1997; 281(1): 304–14PubMedGoogle Scholar
  450. 450.
    Wallace S, Carrier D, Clausen E. Extraction of nutraceuticals from milk thistle: part II. Extraction with organic solvents. Appl Biochem Biotechnol 2003; 108(1–3): 891–904CrossRefGoogle Scholar
  451. 451.
    Barreto J, Wallace S, Carrier D, et al. Extraction of nutraceuticals from milk thistle. I: hot water extraction. Appl Biochem Biotechnol 2003; 108(1–3): 881–90CrossRefGoogle Scholar
  452. 452.
    Wellington K, Jarvis B. Silymarin: a review of its clinical properties in the management of hepatic disorders. Biodrugs 2001; 15(7): 465–89PubMedCrossRefGoogle Scholar
  453. 453.
    Quaglia MG, Bossu E, Donati E, et al. Determination of silymarine in the extract from the dried silybum marianum fruits by high performance liquid chromatography and capillary electrophoresis. J Pharm Biomed Anal 1999; 19(3–4): 435–42PubMedCrossRefGoogle Scholar
  454. 454.
    Kvasnicka F, Biba B, Sevcik R, et al. Analysis of the active components of silymarin. J Chromatogr A 2003; 990(1–2): 239–45PubMedGoogle Scholar
  455. 455.
    Ding T, Tian S, Zhang Z, et al. Determination of active component in silymarin by RP-LC and LC/MS. J Pharm Biomed Anal 2001; 26(1): 155–61PubMedCrossRefGoogle Scholar
  456. 456.
    Lorenz D. Untersuchungen zur elimination von silymarin bei cholezystektomiertan patientsten 2. Mitteilung: Biliaere elimination nach mehrfacher oraler Gabe. Planta Med 1982; 45: 216–23Google Scholar
  457. 457.
    Kren V, Ulrichova J, Kosina P, et al. Chemoenzymatic preparation of silybin beta-glucuronides and their biological evaluation. Drug Metab Dispos 2000; 28(12): 1513–7PubMedGoogle Scholar
  458. 458.
    Weyhenmeyer R, Mascher H, Birkmayer J. Study on doselinearity of the pharmacokinetics of silibinin diastereomers using a new stereospecific assay. Int J Clin Pharmacol Ther Toxicol 1992; 30(4): 134–41PubMedGoogle Scholar
  459. 459.
    Gatti G, Perucca E. Plasma concentrations of free and conjugated silybin after oral intake of a silybin-phosphatidylcholine complex (silipide) in healthy volunteers. Int J Clin Pharmacol Ther 1994; 32(1): 614–7PubMedGoogle Scholar
  460. 460.
    Schandalik R, Gatti G, Perucca E. Pharmacokinetics of silybin in bile following administration of silipide and silymarin in cholecystectomy patients. Arzneimittelforschung 1992; 42(7): 964–8PubMedGoogle Scholar
  461. 461.
    Salmi HA, Sarna S. Effects of silymarin on chemical functional and morphological alterations of the liver. Scand J Gastroenterol 1982; 17: 517–21PubMedCrossRefGoogle Scholar
  462. 462.
    Piscitelli SC, Formentini E, Burstein AH, et al. Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy 2002; 22(5): 551–6PubMedCrossRefGoogle Scholar
  463. 463.
    DiCenzo R, Shelton M, Jordan K, et al. Coadministration of milk thistle and indinavir in healthy subjects. Pharmacotherapy 2003; 23(7): 866–70PubMedCrossRefGoogle Scholar
  464. 464.
    Beckmann-Knopp S, Rietbrock S, Weyhenmeyer R, et al. Inhibitory effects of silibinin on cytochrome P-450 enzymes in human liver microsomes. Pharmacol Toxicol 2000; 86(6): 250–6PubMedCrossRefGoogle Scholar
  465. 465.
    Venkataramanan R, Ramachandran V, Komoroski BJ, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 2000; 28(11): 1270–3PubMedGoogle Scholar
  466. 466.
    Sridar C, Goosen TC, Kent UM, et al. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 2004; 32(6): 587–94PubMedCrossRefGoogle Scholar
  467. 467.
    Schandalik R, Perucca E. Pharmacokinetics of silybin following oral administration of silipide in patients with extrahepatic biliary obstruction. Drugs Exp Clin Res 1994; 20(1): 37–42PubMedGoogle Scholar
  468. 468.
    Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther 2004; 76(5): 428–40PubMedCrossRefGoogle Scholar
  469. 469.
    Zhang S, Morris ME. Effects of the flavonoids biochanin A, morin, phloretin, and silymarin on P-glycoprotein-mediated transport. J Pharmacol Exp Ther 2003; 304(3): 1258–67PubMedCrossRefGoogle Scholar
  470. 470.
    Tyagi AK, Singh RP, Agarwal C, et al. Silibinin strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth Inhibition, G2-M arrest, and apoptosis. Clin Cancer Res 2002; 8(11): 3512–9PubMedGoogle Scholar
  471. 471.
    Maitrejean M, Comte G, Barron D, et al. The flavanolignan silybin and its hemisynthetic derivatives, a novel series of potential modulators of P-glycoprotein. Bioorg Med Chem Lett 2000; 10(2): 157–60PubMedCrossRefGoogle Scholar
  472. 472.
    Schlichting J, Leuschner U. Drug therapy of primary biliary diseases: classical and modern strategies. J Cell Mol Med 2001; 5(1): 98–115PubMedCrossRefGoogle Scholar
  473. 473.
    Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology 2002; 36(3): 525–31PubMedCrossRefGoogle Scholar
  474. 474.
    Angulo P, Patel T, Jorgensen RA, et al. Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid. Hepatology 2000; 32(5): 897–900PubMedCrossRefGoogle Scholar
  475. 475.
    Ellis GR, Stephens MR. Untitled [photograph and brief case report]. BMJ 1999; 319: 650CrossRefGoogle Scholar
  476. 476.
    Deahl M. Betel nut-induced extrapyramidal syndrome: an unusual drug interaction. Mov Disord 1989; 4(4): 330–2PubMedCrossRefGoogle Scholar
  477. 477.
    Mathews Jr MK. Association of Ginkgo biloba with intracerebral haemorrhage [letter]. Neurology 1998; 50(6): 1933–4CrossRefGoogle Scholar
  478. 478.
    Rey JM, Walter G. Hypericum perforatum (St John’s wort) in depression: pest or blessing? Med J Aust 1998; 169(11–12): 583–6PubMedGoogle Scholar
  479. 479.
    Bon S, Hartmann K, Kubn M. Johanniskraut: ein enzyminduktor? Schweitz Apoth Ztg 1999; 16: 535–6Google Scholar
  480. 480.
    Breidenbach T, Hoffmann MW, Becker T, et al. Drug interaction of St John’s wort with cyclosporin [letter]. Lancet 2000: 355(9218): 1912PubMedCrossRefGoogle Scholar
  481. 481.
    Roots I, Johne A, Maurer A. Arzneimittel interaktionen von hypericum-extract [abstract]. In: Roots I, Kemper FH, editors. Proc Germ Soc Pharmacol. Berlin: Conference Organising Committee, 2000 Jun 16–17Google Scholar
  482. 482.
    Barone GW, Gurley BJ, Ketel BL, et al. Herbal supplements: a potential for drug interactions in transplant recipients. Transplantation 2001; 71(2): 239–41PubMedCrossRefGoogle Scholar
  483. 483.
    Khawaja IS, Marotta RF, Lippmann S. Herbal medicines as a factor in delirium. Psychiatr Serv 1999; 50(7): 969–70PubMedGoogle Scholar
  484. 484.
    Valenzuela A, Bustamante JC, Videla C, et al. Effect of silybin dihemisuccinate on the ethanol metabolizing systems of the rat liver. Cell Biochem Funct 1989; 7(3): 173–8PubMedCrossRefGoogle Scholar
  485. 485.
    Comoglio A, Tomasi A, Malandrino S, et al. Scavenging effect of silipide, a new silybin-phospholipid complex, on ethanol-derived free radicals. Biochem Pharmacol 1995; 50(8): 1313–6PubMedCrossRefGoogle Scholar
  486. 486.
    Varga M, Buris L, Fodor M. Ethanol elimination in man under influence of hepatoprotective silibinin. Blutalkohol 1991; 28(6): 405–8PubMedGoogle Scholar
  487. 487.
    Gyonos I, Agoston M, Kovacs A, et al. Silymarin and vitamin E do not attenuate and vitamin E might even enhance the antiarrhythmic activity of amiodarone in a rat reperfusion arrhythmia model. Cardiovasc Drugs Ther 2001; 15(3): 233–40PubMedCrossRefGoogle Scholar
  488. 488.
    Gill J, Heel RC, Fitton A. Amiodarone: an overview of its pharmacological properties, and review of its therapeutic use in cardiac arrhythmias. Drugs 1992; 43(1): 69–110PubMedCrossRefGoogle Scholar
  489. 489.
    Trivier J–M, Libersa C, Belloc C, et al. Amiodarone N-deethylation in human liver microsomes: involvement of cytochrome P4503A enzymes (first report). Life Sci 1993; 52(10): 91–6Google Scholar
  490. 490.
    Fabre G, Julian B, Saint-Aubert B, et al. Evidence for CYP3A-mediated N-deethylation of amiodarone in human liver microsomal fractions. Drug Metab Dispos 1993; 21(6): 978–85PubMedGoogle Scholar
  491. 491.
    Ohyama K, Nakajima M, Nakamura S, et al. A significant role of human cytochrome P4502C8 in amiodarone N-deethylation: an approach to predict the contribution with relative activity factor. Drug Metab Dispos 2000; 28(11): 1303–10PubMedGoogle Scholar
  492. 492.
    Scambia G, De Vincenzo R, Ranelletti FO, et al. Antiproliferative effect of silybin on gynaecological malignancies: synergism with cisplatin and doxorubicin. Eur J Cancer 1996; 32A(5): 877–82PubMedCrossRefGoogle Scholar
  493. 493.
    Giacomelli S, Gallo D, Apollonio P, et al. Silybin and its bioavailable phospholipid complex (IdB 1016) potentiate in vitro and in vivo the activity of cisplatin. Life Sci 2002; 70(12): 1447–59PubMedCrossRefGoogle Scholar
  494. 494.
    Bokemeyer C, Fels LM, Dunn T, et al. Silibinin protects against cisplatin-induced nephrotoxicity without compromising cisplatin or ifosfamide anti-tumour activity. Br J Cancer 1996; 74(12): 2036–41PubMedCrossRefGoogle Scholar
  495. 495.
    Gaedeke J, Fels LM, Bokemeyer C, et al. Cisplatin nephrotoxicity and protection by silibinin. Nephrol Dial Transplant 1996: 11(1): 55–62PubMedCrossRefGoogle Scholar
  496. 496.
    Shelley MD, Burgon K, Mason MD. Treatment of testicular germ-cell cancer: a cochrane evidence-based systematic review. Cancer Treat Rev 2002; 28(5): 237–53PubMedCrossRefGoogle Scholar
  497. 497.
    Sandercock J, Parmar MK, Torri V, et al. First-line treatment for advanced ovarian cancer: paclitaxel, platinum and the evidence. Br J Cancer 2002; 87(8): 815–24PubMedCrossRefGoogle Scholar
  498. 498.
    Piccart MJ, Lamb H, Vermorken JB. Current and future potential roles of the platinum drugs in the treatment of ovarian cancer. Ann Oncol 2001; 12(9): 1195–203PubMedCrossRefGoogle Scholar
  499. 499.
    Go RS, Adjei AA. Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin. J Clin Oncol 1999; 17(1): 409–22PubMedGoogle Scholar
  500. 500.
    Zima T, Kamenikova L, Janebova M, et al. The effect of silibinin on experimental cyclosporine nephrotoxicity. Ren Fail 1998; 20(3): 471–9PubMedCrossRefGoogle Scholar
  501. 501.
    von Schonfeld J, Weisbrod B, Muller MK. Silibinin, a plant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A toxicity. Cell Mol Life Sci 1997; 53(11–12): 917–20CrossRefGoogle Scholar
  502. 502.
    Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet 2000; 38(1): 41–57PubMedCrossRefGoogle Scholar
  503. 503.
    Zhou S, Gao Y, Jiang W, et al. Interactions of herbs with cytochrome P450. Drug Metab Rev 2003; 35(1): 35–98PubMedCrossRefGoogle Scholar
  504. 504.
    Zhou S, Lim LY, Chowbay B. Herbal modulation of P-glycoprotein. Drug Metab Rev 2004; 36(1): 57–104PubMedCrossRefGoogle Scholar
  505. 505.
    Zhou S, Chan E, Li SC, et al. Predicting pharmacokinetic herbdrug interactions. Drug Metabol Drug Interact 2004; 20(3): 143–58PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Zeping Hu
    • 1
  • Xiaoxia Yang
    • 1
  • Paul Chi Lui Ho
    • 1
  • Sui Yung Chan
    • 1
  • Paul Wan Sia Heng
    • 1
  • Eli Chan
    • 1
  • Wei Duan
    • 2
  • Hwee Ling Koh
    • 1
  • Shufeng Zhou
    • 1
    Email author
  1. 1.Department of Pharmacy, Faculty of ScienceNational University of SingaporeSingapore
  2. 2.Department of Biochemistry, Faculty of MedicineNational University of SingaporeSingapore

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