Clinical Pharmacokinetics

, Volume 51, Issue 2, pp 77–104 | Cite as

Drug Interactions with Herbal Medicines

Review Article

Abstract

In recent years, the issue of herbal medicine-drug interactions has generated significant concern. Such interactions can increase the risk for an individual patient, especially with regard to drugs with a narrow therapeutic index (e.g. warfarin, ciclosporin and digoxin). The present article summarizes herbal medicine-drug interactions involving mainly inhibition or induction of cytochrome P450 enzymes and/or drug transporters. An increasing number of in vitro and animal studies, case reports and clinical trials evaluating such interactions have been reported, and the majority of the interactions may be difficult to predict. Potential pharmacodynamic and/or pharmacokinetic interactions of commonly used herbal medicines (black cohosh, garlic, Ginkgo, goldenseal, kava, milk thistle, Panax ginseng, Panax quinquefolius, saw palmetto and St John’s wort) with conventional drugs are presented, and sometimes the results are contradictory. Clinical implications of herbal medicine-drug interactions depend on a variety of factors, such as the co-administered drugs, the patient characteristics, the origin of the herbal medicines, the composition of their constituents and the applied dosage regimens. To optimize the use of herbal medicines, further controlled studies are urgently needed to explore their potential for interactions with conventional drugs and to delineate the underlying mechanisms.

Notes

Acknowledgements

This work was supported by the Natural Science Foundation of Hubei Province (P.R. China) [grant no. 2009CDB380], the Fundamental Research Funds for the Central Universities (P.R. China) [grant no. 2011JC039] and the Robert Bosch Foundation (Stuttgart, Germany).

The authors declare no conflicts of interest.

References

  1. 1.
    Butterweck V, Derendorf H. Potential of pharmacokinetic profiling for detecting herbal interactions with drugs. Clin Pharmacokinet 2008; 47(6): 383–97PubMedCrossRefGoogle Scholar
  2. 2.
    Tarirai C, Viljoen AM, Hamman JH. Herb-drug pharmacokinetic interactions reviewed. Expert Opin Drug Metab Toxicol 2010 Dec; 6(12): 1515–38PubMedCrossRefGoogle Scholar
  3. 3.
    Unger M. Pharmacokinetic drug interactions by herbal drugs: critical evaluation and clinical relevance. Wien Med Wochenschr 2010 Dec; 160(21-22): 571–7PubMedCrossRefGoogle Scholar
  4. 4.
    McFadden R, Peterson N. Interactions between drugs and four common medicinal herbs. Nurs Stand 2011 Jan; 25(19): 65–8PubMedGoogle Scholar
  5. 5.
    Hu Z, Yang X, Ho PC, et al. Herb-drug interactions: a literature review. Drugs 2005; 65(9): 1239–82PubMedCrossRefGoogle Scholar
  6. 6.
    Chavez ML, Jordan MA, Chavez PI. Evidence-based drug-herbal interactions. Life Sci 2006 Mar; 78(18): 2146–57PubMedCrossRefGoogle Scholar
  7. 7.
    Skalli S, Zaid A, Soulaymani R. Drug interactions with herbal medicines. Ther Drug Monit 2007 Dec; 29(6): 679–86PubMedCrossRefGoogle Scholar
  8. 8.
    Gardiner P, Phillips R, Shaughnessy AF. Herbal and dietary supplement-drug interactions in patients with chronic illnesses. Am Fam Physician 2008 Jan; 77(1): 73–8PubMedGoogle Scholar
  9. 9.
    Ulbricht C, Chao W, Costa D, et al. Clinical evidence of herb-drug interactions: a systematic review by the natural standard research collaboration. Curr Drug Metab 2008 Dec; 9(10): 1063–120PubMedCrossRefGoogle Scholar
  10. 10.
    Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs 2009; 69(13): 1777–98PubMedCrossRefGoogle Scholar
  11. 11.
    Remirez D, Avila Pérez J, Jiménez López G, et al. Interactions between herbal remedies and medicinal drugs: considerations about Cuba. Drug Metabol Drug Interact 2009; 24(2–4): 183–94PubMedGoogle Scholar
  12. 12.
    Kennedy DA, Seely D. Clinically based evidence of drug-herb interactions: a systematic review. Expert Opin Drug Saf 2010 Jan; 9(1): 79–124PubMedCrossRefGoogle Scholar
  13. 13.
    Hafner-Blumenstiel V. Herbal drug-drug interaction and adverse drug reactions. Ther Umsch 2011 Jan; 68(1): 54–7PubMedCrossRefGoogle Scholar
  14. 14.
    Paoletti A, Gallo E, Benemei S, et al. Interactions between natural health products and oral anticoagulants: spontaneous reports in the Italian Surveillance System of Natural Health Products. Evid Based Complement Alternat Med 2011; 2011: 612150PubMedCrossRefGoogle Scholar
  15. 15.
    Tachjian A, Maria V, Jahangir A. Use of herbal products and potential interactions in patients with cardiovascular diseases. J Am Coll Cardiol 2010 Feb; 55(6): 515–25PubMedCrossRefGoogle Scholar
  16. 16.
    Colalto C. Herbal interactions on absorption of drugs: mechanisms of action and clinical risk assessment. Pharmacol Res 2010 Sep; 62(3): 207–27PubMedCrossRefGoogle Scholar
  17. 17.
    American Botanical Council. Herbal supplement sales rise in all channels in 2009. Herbalgram 2010; 86: 62–5Google Scholar
  18. 18.
    Asdaq SM, Inamdar MN. Potential of garlic and its active constituent, S-allyl cysteine, as antihypertensive and cardioprotective in presence of captopril. Phytomedicine 2010 Nov; 17(13): 1016–26PubMedCrossRefGoogle Scholar
  19. 19.
    Gharagozloo M, Moayedi B, Zakerinia M, et al. Combined therapy of silymarin and desferrioxamine in patients with beta-thalassemia major: a randomized double-blind clinical trial. Fundam Clin Pharmacol 2009 Jun; 23(3): 359–65PubMedCrossRefGoogle Scholar
  20. 20.
    Saxena A, Tripathi KP, Roy S, et al. Pharmacovigilance: effects of herbal components on human drugs interactions involving cytochrome P450. Bioinformation 2008; 3(5): 198–204PubMedCrossRefGoogle Scholar
  21. 21.
    Kalra BS. Cytochrome P450 enzyme isoforms and their therapeutic implications: an update. Indian J Med Sci 2007 Feb; 61(2): 102–16PubMedCrossRefGoogle Scholar
  22. 22.
    Pelkonen O, Turpeinen M, Hakkola J, et al. Inhibition and induction of human cytochrome P450 enzymes: current status. Arch Toxicol 2008 Oct; 82(10): 667–715PubMedCrossRefGoogle Scholar
  23. 23.
    Zhou S, Koh HL, Gao Y, et al. Herbal bioactivation: the good, the bad and the ugly. Life Sci 2004 Jan; 74(8): 935–68PubMedCrossRefGoogle Scholar
  24. 24.
    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 Jul; 294(1): 88–95PubMedGoogle Scholar
  25. 25.
    Zhou S, Chan E, Lim LY, et al. Therapeutic drugs that behave as mechanism-based inhibitors of cytochrome P450 3A4. Curr Drug Metab 2004 Oct; 5(5): 415–42PubMedCrossRefGoogle Scholar
  26. 26.
    Taesotikul T, Dumrongsakulchai W, Wattanachai N, et al. Inhibitory effects of Phyllanthus amarus and its major lignans on human microsomal cytochrome P450 activities: evidence for CYP3A4 mechanism-based inhibition. Drug Metab Pharmacokinet 2011; 26(2): 154–61PubMedCrossRefGoogle Scholar
  27. 27.
    Zhou S, Chan E, Li X, et al. Clinical outcomes and management of mechanism-based inhibition of cytochrome P450 3A4. Ther Clin Risk Manag 2005 Mar; 1(1): 3–13PubMedCrossRefGoogle Scholar
  28. 28.
    Zhou SF, Xue CC, Yu XQ, et al. Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring. Ther Drug Monit 2007 Dec; 29(6): 687–710PubMedCrossRefGoogle Scholar
  29. 29.
    Lin JH. CYP induction-mediated drug interactions: in vitro assessment and clinical implications. Pharm Res 2006 Jun; 23(6): 1089–116PubMedCrossRefGoogle Scholar
  30. 30.
    Lin JH. Transporter-mediated drug interactions: clinical implications and in vitro assessment. Expert Opin Drug Metab Toxicol 2007 Feb; 3(1): 81–92PubMedCrossRefGoogle Scholar
  31. 31.
    Tirona RG, Bailey DG. Herbal product-drug interactions mediated by induction. Br J Clin Pharmacol 2006 Jun; 61(6): 677–81PubMedCrossRefGoogle Scholar
  32. 32.
    Tompkins LM, Wallace AD. Mechanisms of cytochrome P450 induction. J Biochem Mol Toxicol 2007; 21(4): 176–81PubMedCrossRefGoogle Scholar
  33. 33.
    Jana S, Paliwal J. Molecular mechanisms of cytochrome p450 induction: potential for drug-drug interactions. Curr Protein Pept Sci 2007 Dec; 8(6): 619–28PubMedCrossRefGoogle Scholar
  34. 34.
    Hewitt NJ, Lecluyse EL, Ferguson SS. Induction of hepatic cytochrome P450 enzymes: methods, mechanisms, recommendations, and in vitro-in vivo correlations. Xenobiotica 2007 Oct-Nov; 37(10-11): 1196–224PubMedCrossRefGoogle Scholar
  35. 35.
    Pang X, Cheng J, Krausz KW, et al. Pregnane X receptor-mediated induction of Cyp3a by black cohosh. Xenobiotica 2011 Feb; 41(2): 112–23PubMedCrossRefGoogle Scholar
  36. 36.
    Marquez B, Van Bambeke F. ABC multidrug transporters: target for modulation of drug pharmacokinetics and drug-drug interactions. Curr Drug Targets 2011 May; 12(5): 600–20PubMedCrossRefGoogle Scholar
  37. 37.
    Kota BP, Tran VH, Allen J, et al. Characterization of PXR mediated P-glycoprotein regulation in intestinal LS174T cells. Pharmacol Res 2010 Nov; 62(5): 426–31PubMedCrossRefGoogle Scholar
  38. 38.
    Marchetti S, Mazzanti R, Beijnen JH, et al. Concise review: clinical relevance of drug drug and herb drug interactions mediated by the ABC transporter ABCB1 (MDR1, P-glycoprotein). Oncologist 2007 Aug; 12(8): 927–41PubMedCrossRefGoogle Scholar
  39. 39.
    Pal D, Mitra AK. MDR- and CYP3A4-mediated drug-herbal interactions. Life Sci 2006 Mar 27; 78(18): 2131–45PubMedCrossRefGoogle Scholar
  40. 40.
    Tachibana T, Kato M, Takano J, et al. Predicting drug-drug interactions involving the inhibition of intestinal CYP3A4 and P-glycoprotein. Curr Drug Metab 2010 Nov; 11(9): 762–77PubMedCrossRefGoogle Scholar
  41. 41.
    Tachibana T, Kato M, Watanabe T, et al. Method for predicting the risk of drug-drug interactions involving inhibition of intestinal CYP3A4 and P-glycoprotein. Xenobiotica 2009 Jun; 39(6): 430–43PubMedCrossRefGoogle Scholar
  42. 42.
    Benet LZ. The drug transporter-metabolism alliance: uncovering and defining the interplay. Mol Pharm 2009 Nov-Dec; 6(6): 1631–43PubMedCrossRefGoogle Scholar
  43. 43.
    Zhang L, Zhang Y, Huang SM. Scientific and regulatory perspectives on metabolizing enzyme-transporter interplay and its role in drug interactions: challenges in predicting drug interactions. Mol Pharm 2009 Nov-Dec; 6(6): 1766–74PubMedCrossRefGoogle Scholar
  44. 44.
    Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005 May; 77(5): 415–26PubMedCrossRefGoogle Scholar
  45. 45.
    Gurley BJ, Swain A, Hubbard MA, et al. Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St John’s wort, and Echinacea. Mol Nutr Food Res 2008 Jul; 52(7): 755–63PubMedCrossRefGoogle Scholar
  46. 46.
    Gurley BJ, Barone GW, Williams DK, et al. Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos 2006 Jan; 34(1): 69–74PubMedCrossRefGoogle Scholar
  47. 47.
    Gurley B, Hubbard MA, Williams DK, et al. Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: comparison of a milk thistle and black cohosh product to rifampin and clarithromycin. J Clin Pharmacol 2006 Feb; 46(2): 201–13PubMedCrossRefGoogle Scholar
  48. 48.
    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 Nov; 76(5): 428–40PubMedCrossRefGoogle Scholar
  49. 49.
    Gorski JC, Huang SM, Pinto A, et al. The effect of Echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo. Clin Pharmacol Ther 2004 Jan; 75(1): 89–100PubMedCrossRefGoogle Scholar
  50. 50.
    Molto J, Valle M, Miranda C, et al. Herb-drug interaction between Echinacea purpurea and darunavir-ritonavir in HIV-infected patients. Antimicrob Agents Chemother 2011 Jan; 55(1): 326–30PubMedCrossRefGoogle Scholar
  51. 51.
    Gurley BJ, Swain A, Williams DK, et al. Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St John’s wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics. Mol Nutr Food Res 2008 Jul; 52(7): 772–9PubMedCrossRefGoogle Scholar
  52. 52.
    Penzak SR, Robertson SM, Hunt JD, et al. Echinacea purpurea significantly induces cytochrome P450 3A activity but does not alter lopinavir-ritonavir exposure in healthy subjects. Pharmacotherapy 2010 Aug; 30(8): 797–805PubMedCrossRefGoogle Scholar
  53. 53.
    Abdul MI, Jiang X, Williams KM, et al. Pharmacokinetic and pharmacodynamic interactions of Echinacea and policosanol with warfarin in healthy subjects. Br J Clin Pharmacol 2010 May; 69(5): 508–15PubMedCrossRefGoogle Scholar
  54. 54.
    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 Aug; 74(2): 170–7PubMedCrossRefGoogle Scholar
  55. 55.
    Gurley BJ, Gardner SF, Hubbard MA, et al. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John’s wort, garlic oil, Panax ginseng and Ginkgo biloba. Drugs Aging 2005; 22(6): 525–39PubMedCrossRefGoogle Scholar
  56. 56.
    Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002 Sep; 72(3): 276–87PubMedCrossRefGoogle Scholar
  57. 57.
    Loizou GD, Cocker J. The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazone. Hum Exp Toxicol 2001 Jul; 20(7): 321–7PubMedCrossRefGoogle Scholar
  58. 58.
    Jabbari A, Argani H, Ghorbanihaghjo A, et al. Comparison between swallowing and chewing of garlic on levels of serum lipids, cyclosporine, creatinine and lipid peroxidation in renal transplant recipients. Lipids Health Dis 2005 May; 4: 11PubMedCrossRefGoogle Scholar
  59. 59.
    Cox MC, Low J, Lee J, et al. Influence of garlic (Allium sativum) on the pharmacokinetics of docetaxel. Clin Cancer Res 2006 Aug; 12(15): 4636–40PubMedCrossRefGoogle Scholar
  60. 60.
    Pathak A, Leger P, Bagheri H, et al. Garlic interaction with fluindione: a case report. Therapie 2003 Jul-Aug; 58(4): 380–1PubMedCrossRefGoogle Scholar
  61. 61.
    Gwilt PR, Lear CL, Tempero MA, et al. The effect of garlic extract on human metabolism of acetaminophen. Cancer Epidemiol Biomarkers Prev 1994 Mar; 3(2): 155–60PubMedGoogle Scholar
  62. 62.
    Hajda J, Rentsch KM, Gubler C, et al. Garlic extract induces intestinal P-glycoprotein, but exhibits no effect on intestinal and hepatic CYP3A4 in humans. Eur J Pharm Sci 2010 Dec; 41(5): 729–35PubMedCrossRefGoogle Scholar
  63. 63.
    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 Feb; 55(2): 199–202PubMedCrossRefGoogle Scholar
  64. 64.
    Piscitelli SC, Burstein AH, Welden N, et al. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 2002 Jan; 34(2): 234–8PubMedCrossRefGoogle Scholar
  65. 65.
    Evans V. Herbs and the brain: friend or foe? The effects of Ginkgo and garlic on warfarin use. J Neurosci Nurs 2000 Aug; 32(4): 229–32PubMedCrossRefGoogle Scholar
  66. 66.
    Mohammed Abdul MI, Jiang X, Williams KM, et al. Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects. Br J Pharmacol 2008 Aug; 154(8): 1691–700PubMedCrossRefGoogle Scholar
  67. 67.
    Macan H, Uykimpang R, Alconcel M, et al. Aged garlic extract may be safe for patients on warfarin therapy. J Nutr 2006 Mar; 136(3 Suppl.): 793S–5SPubMedGoogle Scholar
  68. 68.
    Markowitz JS, Donovan JL, Lindsay DC, et al. Multiple-dose administration of Ginkgo biloba did not affect cytochrome P-450 2D6 or 3A4 activity in normal volunteers. J Clin Psychopharmacol 2003 Dec; 23(6): 576–81PubMedCrossRefGoogle Scholar
  69. 69.
    Lei HP, Ji W, Lin J, et al. Effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy volunteers. Br J Clin Pharmacol 2009 Aug; 68(2): 201–6PubMedCrossRefGoogle Scholar
  70. 70.
    Aruna D, Naidu MU. Pharmacodynamic interaction studies of Ginkgo biloba with cilostazol and clopidogrel in healthy human subjects. Br J Clin Pharmacol 2007 Mar; 63(3): 333–8PubMedCrossRefGoogle Scholar
  71. 71.
    Zuo XC, Zhang BK, Jia SJ, et al. Effects of Ginkgo biloba extracts on diazepam metabolism: a pharmacokinetic study in healthy Chinese male subjects. Eur J Clin Pharmacol 2010 May; 66(5): 503–9PubMedCrossRefGoogle Scholar
  72. 72.
    Mohutsky MA, Anderson GD, Miller JW, et al. Ginkgo biloba: evaluation of CYP2C9 drug interactions in vitro and in vivo. Am J Ther 2006 Jan-Feb; 13(1): 24–31PubMedCrossRefGoogle Scholar
  73. 73.
    Mauro VF, Mauro LS, Kleshinski JF, et al. Impact of Ginkgo biloba on the pharmacokinetics of digoxin. Am J Ther 2003 Jul-Aug; 10(4): 247–51PubMedCrossRefGoogle Scholar
  74. 74.
    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 May; 44(5): 538–42PubMedCrossRefGoogle Scholar
  75. 75.
    Robertson SM, Davey RT, Voell J, et al. Effect of Ginkgo biloba extract on lopinavir, midazolam and fexofenadine pharmacokinetics in healthy subjects. Curr Med Res Opin 2008 Feb; 24(2): 591–9PubMedCrossRefGoogle Scholar
  76. 76.
    Kim KA, Park PW, Park JY. Short-term effect of quercetin on the pharmacokinetics of fexofenadine, a substrate of P-glycoprotein, in healthy volunteers. Eur J Clin Pharmacol 2009 Jun; 65(6): 609–14PubMedCrossRefGoogle Scholar
  77. 77.
    Greenblatt DJ, von Moltke LL, Luo Y, et al. Ginkgo biloba does not alter clearance of flurbiprofen, a cytochrome P450-2C9 substrate. J Clin Pharmacol 2006 Feb; 46(2): 214–21PubMedCrossRefGoogle Scholar
  78. 78.
    Kudolo GB, Wang W, Javors M, et al. The effect of the ingestion of Ginkgo biloba extract (EGb 761) on the pharmacokinetics of metformin in non-diabetic and type 2 diabetic subjects: a double blind placebo-controlled, crossover study. Clin Nutr 2006 Aug; 25(4): 606–16PubMedCrossRefGoogle Scholar
  79. 79.
    Uchida S, Yamada H, Li XD, et al. Effects of Ginkgo biloba extract on pharmacokinetics and pharmacodynamics of tolbutamide and midazolam in healthy volunteers. J Clin Pharmacol 2006 Nov; 46(11): 1290–8PubMedCrossRefGoogle Scholar
  80. 80.
    Yoshioka M, Ohnishi N, Koishi T, et al. Studies on interactions between functional foods or dietary supplements and medicines: IV. Effects of Ginkgo biloba leaf extract on the pharmacokinetics and pharmacodynamics of nifedipine in healthy volunteers. Biol Pharm Bull 2004 Dec; 27(12): 2006–9PubMedCrossRefGoogle Scholar
  81. 81.
    Yin OQ, Tomlinson B, Waye MM, et al. Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole. Pharmacogenetics 2004 Dec; 14(12): 841–50PubMedCrossRefGoogle Scholar
  82. 82.
    Fan L, Tao GY, Wang G, et al. Effects of Ginkgo biloba extract ingestion on the pharmacokinetics of talinolol in healthy Chinese volunteers. Ann Pharmacother 2009 May; 43(5): 944–9PubMedCrossRefGoogle Scholar
  83. 83.
    Fan L, Mao XQ, Tao GY, et al. Effect of Schisandra chinensis extract and Ginkgo biloba extract on the pharmacokinetics of talinolol in healthy volunteers. Xenobiotica 2009 Mar; 39(3): 249–54PubMedCrossRefGoogle Scholar
  84. 84.
    Kim BH, Kim KP, Lim KS, et al. Influence of Ginkgo biloba extract on the pharmacodynamic effects and pharmacokinetic properties of ticlopidine: an open-label, randomized, two-period, two-treatment, two-sequence, single-dose crossover study in healthy Korean male volunteers. Clin Ther 2010 Feb; 32(2): 380–90PubMedCrossRefGoogle Scholar
  85. 85.
    Kim TE, Kim BH, Kim J, et al. Comparison of the pharmacokinetics of ticlopidine between administration of a combined fixed-dose tablet formulation of ticlopidine 250 mg/Ginkgo extract 80 mg, and concomitant administration of ticlopidine 250-mg and Ginkgo extract 80-mg tablets: an open-label, two-treatment, single-dose, randomized-sequence crossover study in healthy Korean male volunteers. Clin Ther 2009 Oct; 31(10): 2249–57PubMedCrossRefGoogle Scholar
  86. 86.
    Lu WJ, Huang JD, Lai ML. The effects of ergoloid mesylates and Ginkgo biloba on the pharmacokinetics of ticlopidine. J Clin Pharmacol 2006 Jun; 46(6): 628–34PubMedCrossRefGoogle Scholar
  87. 87.
    Lei HP, Wang G, Wang LS, et al. Lack of effect of Ginkgo biloba on voriconazole pharmacokinetics in Chinese volunteers identified as CYP2C19 poor and extensive metabolizers. Ann Pharmacother 2009 Apr; 43(4): 726–31PubMedCrossRefGoogle Scholar
  88. 88.
    Jiang X, Williams KM, Liauw WS, et al. Effect of Ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2005 Apr; 59(4): 425–32PubMedCrossRefGoogle Scholar
  89. 89.
    Xin HW, Wu XC, Li Q, et al. The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers. Methods Find Exp Clin Pharmacol 2006 Jan-Feb; 28(1): 25–9PubMedCrossRefGoogle Scholar
  90. 90.
    Wu X, Li Q, Xin H, et al. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol 2005 Sep; 61(8): 567–72PubMedCrossRefGoogle Scholar
  91. 91.
    Gurley BJ, Swain A, Barone GW, et al. Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos 2007 Feb; 35(2): 240–5PubMedCrossRefGoogle Scholar
  92. 92.
    Sandhu RS, Prescilla RP, Simonelli TM, et al. Influence of goldenseal root on the pharmacokinetics of indinavir. J Clin Pharmacol 2003 Nov; 43(11): 1283–8PubMedCrossRefGoogle Scholar
  93. 93.
    Gurley BJ, Swain A, Hubbard MA, et al. Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo. Clin Pharmacol Ther 2008 Jan; 83(1): 61–9PubMedCrossRefGoogle Scholar
  94. 94.
    Schelosky L, Raffauf C, Jendroska K, et al. Kava and dopamine antagonism. J Neurol Neurosurg Psychiatry 1995 May; 58(5): 639–40PubMedCrossRefGoogle Scholar
  95. 95.
    DiCenzo R, Shelton M, Jordan K, et al. Coadministration of milk thistle and indinavir in healthy subjects. Pharmacotherapy 2003 Jul; 23(7): 866–70PubMedCrossRefGoogle Scholar
  96. 96.
    Piscitelli SC, Formentini E, Burstein AH, et al. Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy 2002 May; 22(5): 551–6PubMedCrossRefGoogle Scholar
  97. 97.
    Mills E, Wilson K, Clarke M, et al. Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis. Eur J Clin Pharmacol 2005 Mar; 61(1): 1–7PubMedCrossRefGoogle Scholar
  98. 98.
    van Erp NP, Baker SD, Zhao M, et al. Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clin Cancer Res 2005 Nov; 11(21): 7800–6PubMedCrossRefGoogle Scholar
  99. 99.
    Han Y, Guo D, Chen Y, et al. Effect of silymarin on the pharmacokinetics of losartan and its active metabolite E-3174 in healthy Chinese volunteers. Eur J Clin Pharmacol 2009 Jun; 65(6): 585–91PubMedCrossRefGoogle Scholar
  100. 100.
    Rajnarayana K, Reddy MS, Vidyasagar J, et al. Study on the influence of silymarin pretreatment on metabolism and disposition of metronidazole. Arzneimittelforschung 2004; 54(2): 109–13PubMedGoogle Scholar
  101. 101.
    Fuhr U, Beckmann-Knopp S, Jetter A, et al. The effect of silymarin on oral nifedipine pharmacokinetics. Planta Med 2007 Nov; 73(14): 1429–35PubMedCrossRefGoogle Scholar
  102. 102.
    Rao BN, Srinivas M, Kumar YS, et al. Effect of silymarin on the oral bioavailability of ranitidine in healthy human volunteers. Drug Metabol Drug Interact 2007; 22(2-3): 175–85PubMedCrossRefGoogle Scholar
  103. 103.
    Deng JW, Shon JH, Shin HJ, et al. Effect of silymarin supplement on the pharmacokinetics of rosuvastatin. Pharm Res 2008 Aug; 25(8): 1807–14PubMedCrossRefGoogle Scholar
  104. 104.
    Han Y, Guo D, Chen Y, et al. Effect of continuous silymarin administration on oral talinolol pharmacokinetics in healthy volunteers. Xenobiotica 2009 Sep; 39(9): 694–9PubMedCrossRefGoogle Scholar
  105. 105.
    Smith M, Lin KM, Zheng YP. An open trial of nifedipine-herb interactions: nifedipine with St John’s wort, ginseng, or Ginkgo biloba [abstract]. Clin Pharmacol Ther 2001; 69: P86Google Scholar
  106. 106.
    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 May; 57(5): 592–9PubMedCrossRefGoogle Scholar
  107. 107.
    Lee SH, Ahn YM, Ahn SY, et al. Interaction between warfarin and Panax ginseng in ischemic stroke patients. J Altern Complement Med 2008 Jul; 14(6): 715–21PubMedCrossRefGoogle Scholar
  108. 108.
    Lee YH, Lee BK, Choi YJ, et al. Interaction between warfarin and Korean red ginseng in patients with cardiac valve replacement. Int J Cardiol 2010 Nov; 145(2): 275–6PubMedCrossRefGoogle Scholar
  109. 109.
    Andrade AS, Hendrix C, Parsons TL, et al. Pharmacokinetic and metabolic effects of American ginseng (Panax quinquefolius) in healthy volunteers receiving the HIV protease inhibitor indinavir. BMC Complement Altern Med 2008 Aug 19; 8: 50PubMedCrossRefGoogle Scholar
  110. 110.
    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 Jul 6; 141(1): 23–7PubMedGoogle Scholar
  111. 111.
    Lee LS, Wise SD, Chan C, et al. Possible differential induction of phase 2 enzyme and antioxidant pathways by American ginseng, Panax quinquefolius. J Clin Pharmacol 2008 May; 48(5): 599–609PubMedCrossRefGoogle Scholar
  112. 112.
    Markowitz JS, Donovan JL, Devane CL, et al. Multiple doses of saw palmetto (Serenoa repens) did not alter cytochrome P450 2D6 and 3A4 activity in normal volunteers. Clin Pharmacol Ther 2003 Dec; 74(6): 536–42PubMedCrossRefGoogle Scholar
  113. 113.
    Arold G, Donath F, Maurer A, et al. No relevant interaction with alprazolam, caffeine, tolbutamide, and digoxin by treatment with a low-hyperforin St John’s wort extract. Planta Med 2005 Apr; 71(4): 331–7PubMedCrossRefGoogle Scholar
  114. 114.
    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 Jan 21; 66(9): PL133–9PubMedCrossRefGoogle Scholar
  115. 115.
    Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St John’s wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 2003 Sep; 290(11): 1500–4PubMedCrossRefGoogle Scholar
  116. 116.
    Johne A, Schmider J, Brockmöller 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 Feb; 22(1): 46–54PubMedCrossRefGoogle Scholar
  117. 117.
    Andrén L, Andreasson A, Eggertsen R. Interaction between a commercially available St John’s wort product (Movina) and atorvastatin in patients with hypercholesterolemia. Eur J Clin Pharmacol 2007 Oct; 63(10): 913–6PubMedCrossRefGoogle Scholar
  118. 118.
    Lei HP, Yu XY, Xie HT, et al. Effect of St John’s wort supplementation on the pharmacokinetics of bupropion in healthy male Chinese volunteers. Xenobiotica 2010 Apr; 40(4): 275–81PubMedCrossRefGoogle Scholar
  119. 119.
    Dannawi M. Possible serotonin syndrome after combination of buspirone and St John’s wort. J Psychopharmacol 2002 Dec; 16(4): 401PubMedCrossRefGoogle Scholar
  120. 120.
    Wenk M, Todesco L, Krähenbühl S. Effect of St John’s wort on the activities of CYP1A2, CYP3A4, CYP2D6, N-acetyltransferase 2, and xanthine oxidase in healthy males and females. Br J Clin Pharmacol 2004 Apr; 57(4): 495–9PubMedCrossRefGoogle Scholar
  121. 121.
    Wang Z, Gorski JC, Hamman MA, et al. The effects of St John’s wort (Hypericum perforatum) on human cytochrome P450 activity. Clin Pharmacol Ther 2001 Oct; 70(4): 317–26PubMedGoogle Scholar
  122. 122.
    Wang LS, Zhu B, Abd El-Aty AM, et al. The influence of St John’s wort on CYP2C19 activity with respect to genotype. J Clin Pharmacol 2004 Jun; 44(6): 577–81PubMedCrossRefGoogle Scholar
  123. 123.
    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 Dec; 68(6): 605–12PubMedCrossRefGoogle Scholar
  124. 124.
    Johne A, Perloff ES, Bauer S, et al. Impact of cytochrome P-450 inhibition by cimetidine and induction by carbamazepine on the kinetics of hypericin and pseudohypericin in healthy volunteers. Eur J Clin Pharmacol 2004 Nov; 60(9): 617–22PubMedCrossRefGoogle Scholar
  125. 125.
    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 Jan; 73(1): 41–50PubMedCrossRefGoogle Scholar
  126. 126.
    Mai I, Bauer S, Perloff ES, et al. Hyperforin content determines the magnitude of the St John’s wort-cyclosporine drug interaction. Clin Pharmacol Ther 2004 Oct; 76(4): 330–40PubMedCrossRefGoogle Scholar
  127. 127.
    Alscher DM, Klotz U. Drug interaction of herbal tea containing St John’s wort with cyclosporine. Transpl Int 2003 Jul; 16(7): 543–4PubMedCrossRefGoogle Scholar
  128. 128.
    Bauer S, Störmer 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 Feb; 55(2): 203–11PubMedCrossRefGoogle Scholar
  129. 129.
    Roby CA, Dryer DA, Burstein AH. St John’s wort: effect on CYP2D6 activity using dextromethorphan-dextrorphan ratios. J Clin Psychopharmacol 2001 Oct; 21(5): 530–2PubMedCrossRefGoogle Scholar
  130. 130.
    Dürr 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 Dec; 68(6): 598–604PubMedCrossRefGoogle Scholar
  131. 131.
    Mueller SC, Uehleke B, Woehling H, et al. Effect of St John’s wort dose and preparations on the pharmacokinetics of digoxin. Clin Pharmacol Ther 2004 Jun; 75(6): 546–57PubMedCrossRefGoogle Scholar
  132. 132.
    Dasgupta A. Herbal supplements and therapeutic drug monitoring: focus on digoxin immunoassays and interactions with St John’s wort. Ther Drug Monit 2008 Apr; 30(2): 212–7PubMedCrossRefGoogle Scholar
  133. 133.
    Wang Z, Hamman MA, Huang SM, et al. Effect of St John’s wort on the pharmacokinetics of fexofenadine. Clin Pharmacol Ther 2002 Jun; 71(6): 414–20PubMedCrossRefGoogle Scholar
  134. 134.
    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 Mar; 45(3): 352–6PubMedCrossRefGoogle Scholar
  135. 135.
    Lundahl A, Hedeland M, Bondesson U, et al. The effect of St John’s wort on the pharmacokinetics, metabolism and biliary excretion of finasteride and its metabolites in healthy men. Eur J Pharm Sci 2009 Mar; 36(4-5): 433–43PubMedCrossRefGoogle Scholar
  136. 136.
    Bonetto N, Santelli L, Battistin L, et al. Serotonin syndrome and rhabdomyolysis induced by concomitant use of trip tans, fluoxetine and Hypericum. Cephalalgia 2007 Dec; 27(12): 1421–3PubMedCrossRefGoogle Scholar
  137. 137.
    Xu H, Williams KM, Liauw WS, et al. Effects of St John’s wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide. Br J Pharmacol 2008 Apr; 153(7): 1579–86PubMedCrossRefGoogle Scholar
  138. 138.
    Bell EC, Ravis WR, Lloyd KB, et al. Effects of St John’s wort supplementation on ibuprofen pharmacokinetics. Ann Pharmacother 2007 Feb; 41(2): 229–34PubMedCrossRefGoogle Scholar
  139. 139.
    Smith PF, Bullock JM, Booker BM, et al. Induction of imatinib metabolism by Hypericum perforatum. Blood 2004 Aug; 104(4): 1229–30PubMedCrossRefGoogle Scholar
  140. 140.
    Smith P, Bullock JM, Booker BM, et al. The influence of St John’s wort on the pharmacokinetics and protein binding of imatinib mesylate. Pharmacotherapy 2004 Nov; 24(11): 1508–14PubMedCrossRefGoogle Scholar
  141. 141.
    Frye RF, Fitzgerald SM, Lagattuta TF, et al. Effect of St John’s wort on imatinib mesylate pharmacokinetics. Clin Pharmacol Ther 2004 Oct; 76(4): 323–9PubMedCrossRefGoogle Scholar
  142. 142.
    Piscitelli SC, Burstein AH, Chaitt D, et al. Indinavir concentrations and St John’s wort. Lancet 2000 Feb; 355(9203): 547–8PubMedCrossRefGoogle Scholar
  143. 143.
    Mathijssen RH, Verweij J, de Bruijn P, et al. Effects of St John’s wort on irinotecan metabolism. J Natl Cancer Inst 2002 Aug; 94(16): 1247–9PubMedCrossRefGoogle Scholar
  144. 144.
    Portolés A, Terleira A, Calvo A, et al. Effects of Hypericum perforatum on ivabradine pharmacokinetics in healthy volunteers: an open-label, pharmacokinetic interaction clinical trial. J Clin Pharmacol 2006 Oct; 46(10): 1188–94PubMedCrossRefGoogle Scholar
  145. 145.
    Eich-Höchli D, Oppliger R, Golay KP, et al. Methadone maintenance treatment and St John’s wort: a case report. Pharmacopsychiatry 2003 Jan; 36(1): 35–7PubMedCrossRefGoogle Scholar
  146. 146.
    Mueller SC, Majcher-Peszynska J, Uehleke B, et al. The extent of induction of CYP3A by St John’s wort varies among products and is linked to hyperforin dose. Eur J Clin Pharmacol 2006 Jan; 62(1): 29–36PubMedCrossRefGoogle Scholar
  147. 147.
    Mueller SC, Majcher-Peszynska J, Mundkowski RG, et al. No clinically relevant CYP3A induction after St John’s wort with low hyperforin content in healthy volunteers. Eur J Clin Pharmacol 2009 Jan; 65(1): 81–7PubMedCrossRefGoogle Scholar
  148. 148.
    Imai H, Kotegawa T, Tsutsumi K, et al. The recovery time-course of CYP3A after induction by St John’s wort administration. Br J Clin Pharmacol 2008 May; 65(5): 701–7PubMedCrossRefGoogle Scholar
  149. 149.
    Mai I, Störmer 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 Apr; 18(4): 819–22PubMedCrossRefGoogle Scholar
  150. 150.
    St John’s wort found to lower nevirapine levels. TreatmentUpdate 2001; 12: 6Google Scholar
  151. 151.
    de Maat MM, Hoetelmans RM, Matht RA, et al. Drug interaction between St John’s wort and nevirapine. AIDS 2001 Feb; 15(3): 420–1PubMedCrossRefGoogle Scholar
  152. 152.
    Wang XD, Li JL, Su QB, et al. Impact of the haplotypes of the human pregnane X receptor gene on the basal and St John’s wort-induced activity of cytochrome P450 3A4 enzyme. Br J Clin Pharmacol 2009 Feb; 67(2): 255–61PubMedCrossRefGoogle Scholar
  153. 153.
    Wang LS, Zhou G, Zhu B, et al. St John’s wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole. Clin Pharmacol Ther 2004 Mar; 75(3): 191–7PubMedCrossRefGoogle Scholar
  154. 154.
    Will-Shahab L, Bauer S, Kunter U, et al. St John’s wort extract (Ze 117) does not alter the pharmacokinetics of a low-dose oral contraceptive. Eur J Clin Pharmacol 2009 Mar; 65(3): 287–94PubMedCrossRefGoogle Scholar
  155. 155.
    Hall SD, Wang Z, Huang SM, et al. The interaction between St John’s wort and an oral contraceptive. Clin Pharmacol Ther 2003 Dec; 74(6): 525–35PubMedCrossRefGoogle Scholar
  156. 156.
    Murphy PA, Kern SE, Stanczyk FZ, et al. Interaction of St John’s wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. Contraception 2005 Jun; 71(6): 402–8PubMedCrossRefGoogle Scholar
  157. 157.
    Pfrunder A, Schiesser M, Gerber S, et al. Interaction of St John’s wort with low-dose oral contraceptive therapy: a randomized controlled trial. Br J Clin Pharmacol 2003 Dec; 56(6): 683–90PubMedCrossRefGoogle Scholar
  158. 158.
    Fogle RH, Murphy PA, Westhoff CL, et al. Does St John’s wort interfere with the antiandrogenic effect of oral contraceptive pills? Contraception 2006 Sep; 74(3): 245–8PubMedCrossRefGoogle Scholar
  159. 159.
    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 Dec; 70(6): 518–24PubMedCrossRefGoogle Scholar
  160. 160.
    Bell EC, Ravis WR, Chan HM, et al. Lack of pharmacokinetic interaction between St John’s wort and prednisone. Ann Pharmacother 2007 Nov; 41(11): 1819–24PubMedCrossRefGoogle Scholar
  161. 161.
    Kawaguchi A, Ohmori M, Tsuruoka S, et al. Drug interaction between St John’s wort and quazepam. Br J Clin Pharmacol 2004 Oct; 58(4): 403–10PubMedCrossRefGoogle Scholar
  162. 162.
    Hafner V, Jäger M, Matthée AK, et al. Effect of simultaneous induction and inhibition of CYP3A by St John’s wort and ritonavir on CYP3A activity. Clin Pharmacol Ther 2010 Feb; 87(2): 191–6PubMedCrossRefGoogle Scholar
  163. 163.
    Schwarz UI, Hanso H, Oertel R, et al. Induction of intestinal P-glycoprotein by St John’s wort reduces the oral bioavailability of talinolol. Clin Pharmacol Ther 2007 May; 81(5): 669–78PubMedCrossRefGoogle Scholar
  164. 164.
    Hebert MF, Park JM, Chen YL, et al. Effects of St John’s wort (Hypericum perforatum) on tacrolimus pharmacokinetics in healthy volunteers. J Clin Pharmacol 2004 Jan; 44(1): 89–94PubMedCrossRefGoogle Scholar
  165. 165.
    Nebel A, Schneider BJ, Baker RK, et al. Potential metabolic interaction between St John’s wort and theophylline. Ann Pharmacother 1999 Apr; 33(4): 502PubMedCrossRefGoogle Scholar
  166. 166.
    Morimoto T, Kotegawa T, Tsutsumi K, et al. Effect of St John’s wort on the pharmacokinetics of theophylline in healthy volunteers. J Clin Pharmacol 2004 Jan; 44(1): 95–101PubMedCrossRefGoogle Scholar
  167. 167.
    Tannergren C, Engman H, Knutson L, et al. St John’s wort decreases the bioavailability of R- and S-verapamil through induction of the first-pass metabolism. Clin Pharmacol Ther 2004 Apr; 75(4): 298–309PubMedCrossRefGoogle Scholar
  168. 168.
    Xie HG, Kim RB. St John’s wort-associated drug interactions: short-term inhibition and long-term induction? Clin Pharmacol Ther 2005 Jul; 78(1): 19–24PubMedCrossRefGoogle Scholar
  169. 169.
    Rengelshausen J, Banfield M, Riedel KD, et al. Opposite effects of short-term and long-term St John’s wort intake on voriconazole pharmacokinetics. Clin Pharmacol Ther 2005 Jul; 78(1): 25–33PubMedCrossRefGoogle Scholar
  170. 170.
    Hojo Y, Echizenya M, Ohkubo T, et al. Drug interaction between St John’s wort and zolpidem in healthy subjects. J Clin Pharm Ther 2011 Dec; 36(6): 711–5PubMedCrossRefGoogle Scholar
  171. 171.
    Shams T, Setia MS, Hemmings R, et al. Efficacy of black cohosh-containing preparations on menopausal symptoms: a meta-analysis. Altern Ther Health Med 2010 Jan-Feb; 16(1): 36–44PubMedGoogle Scholar
  172. 172.
    Teschke R, Schwarzenboeck A. Suspected hepatotoxicity by Cimicifugae racemosae rhizoma (black cohosh, root): critical analysis and structured causality assessment. Phytomedicine 2009 Jan; 16(1): 72–84PubMedCrossRefGoogle Scholar
  173. 173.
    Naser B, Schnitker J, Minkin MJ, et al. Suspected black cohosh hepatotoxicity: no evidence by meta-analysis of randomized controlled clinical trials for isopropanolic black cohosh extract. Menopause 2011 Apr; 18(4): 366–75PubMedCrossRefGoogle Scholar
  174. 174.
    Teschke R. Black cohosh and suspected hepatotoxicity: inconsistencies, confounding variables, and prospective use of a diagnostic causality algorithm. A critical review. Menopause 2010 Mar; 17(2): 426–40PubMedCrossRefGoogle Scholar
  175. 175.
    Mahady GB, Low DT, Barrett ML, et al. United States Pharmacopeia review of the black cohosh case reports of hepatotoxicity. Menopause 2008 Jul–Aug; 15(4 Pt 1): 628–38PubMedCrossRefGoogle Scholar
  176. 176.
    Huang Y, Jiang B, Nuntanakorn P, et al. Fukinolic acid derivatives and triterpene glycosides from black cohosh inhibit CYP isozymes, but are not cytotoxic to Hep-G2 cells in vitro. Curr Drug Saf 2010 Apr; 5(2): 118–24PubMedCrossRefGoogle Scholar
  177. 177.
    Barrett B, Brown R, Rakel D, et al. Echinacea for treating the common cold: a randomized trial. Ann Intern Med 2010 Dec; 153(12): 769–77PubMedGoogle Scholar
  178. 178.
    Freeman C, Spelman K. A critical evaluation of drug interactions with Echinacea spp. Mol Nutr Food Res 2008 Jul; 52(7): 789–98PubMedCrossRefGoogle Scholar
  179. 179.
    Modarai M, Gertsch J, Suter A, et al. Cytochrome P450 inhibitory action of Echinacea preparations differs widely and co-varies with alkylamide content. J Pharm Pharmacol 2007 Apr; 59(4): 567–73PubMedCrossRefGoogle Scholar
  180. 180.
    Modarai M, Silva E, Suter A, et al. Safety of herbal medicinal products: Echinacea and selected alkylamides do not induce CYP3A4 mRNA expression. Evid Based Complement Alternat Med Epub 2009 Nov 11Google Scholar
  181. 181.
    Modarai M, Yang M, Suter A, et al. Metabolomic profiling of liquid Echinacea medicinal products with in vitro inhibitory effects on cytochrome P450 3A4 (CYP3A4). Planta Med 2010 Mar; 76(4): 378–85PubMedCrossRefGoogle Scholar
  182. 182.
    Hansen TS, Nilsen OG. In vitro CYP3A4 metabolism: inhibition by Echinacea purpurea and choice of substrate for the evaluation of herbal inhibition. Basic Clin Pharmacol Toxicol 2008 Nov; 103(5): 445–9PubMedCrossRefGoogle Scholar
  183. 183.
    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 Jul; 7(4): 273–82PubMedCrossRefGoogle Scholar
  184. 184.
    Yale SH, Glurich I. Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9. J Altern Complement Med 2005 Jun; 11(3): 433–9PubMedCrossRefGoogle Scholar
  185. 185.
    Hellum BH, Hu Z, Nilsen OG. The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in cultured primary human hepatocytes. Basic Clin Pharmacol Toxicol 2007 Jan; 100(1): 23–30PubMedCrossRefGoogle Scholar
  186. 186.
    Hellum BH, Nilsen OG. The in vitro inhibitory potential of trade herbal products on human CYP2D6-mediated metabolism and the influence of ethanol. Basic Clin Pharmacol Toxicol 2007 Nov; 101(5): 350–8PubMedCrossRefGoogle Scholar
  187. 187.
    Hellum BH, Hu Z, Nilsen OG. Trade herbal products and induction of CYP2C19 and CYP2E1 in cultured human hepatocytes. Basic Clin Pharmacol Toxicol 2009 Jul; 105(1): 58–63PubMedCrossRefGoogle Scholar
  188. 188.
    Hellum BH, Nilsen OG. In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol 2008 May; 102(5): 466–75PubMedCrossRefGoogle Scholar
  189. 189.
    Raner GM, Cornelious S, Moulick K, et al. Effects of herbal products and their constituents on human cytochrome P450 (2E1) activity. Food Chem Toxicol 2007 Dec; 45(12): 2359–65PubMedCrossRefGoogle Scholar
  190. 190.
    Mrozikiewicz PM, Bogacz A, Karasiewicz M, et al. The effect of standardized Echinacea purpurea extract on rat cytochrome P450 expression level. Phytomedicine 2010 Aug; 17(10): 830–3PubMedCrossRefGoogle Scholar
  191. 191.
    Hansen TS, Nilsen OG. Echinacea purpurea and P-glycoprotein drug transport in Caco-2 cells. Phytother Res 2009 Jan; 23(1): 86–91PubMedCrossRefGoogle Scholar
  192. 192.
    Romiti N, Pellati F, Nieri P, et al. P-Glycoprotein inhibitory activity of lipophilic constituents of Echinacea pallida roots in a human proximal tubular cell line. Planta Med 2008 Feb; 74(3): 264–6PubMedCrossRefGoogle Scholar
  193. 193.
    Fuchikami H, Satoh H, Tsujimoto M, et al. Effects of herbal extracts on the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos 2006 Apr; 34(4): 577–82PubMedCrossRefGoogle Scholar
  194. 194.
    Singh YP, Singh RA. Insilico studies of organosulfur-functional active compounds in garlic. Biofactors 2010 Jul-Aug; 36(4): 297–311PubMedCrossRefGoogle Scholar
  195. 195.
    Reddy GD, Reddy AG, Rao GS, et al. Interaction study on garlic and atorvastatin with reference to nephrotoxicity in dyslipidaemic rats. Toxicol Int 2010 Jul; 17(2): 90–3PubMedCrossRefGoogle Scholar
  196. 196.
    Asdaq SM, Inamdar MN, Asad M. Pharmacodynamic interaction of garlic with propranolol in ischemia-reperfusion induced myocardial damage. Pak J Pharm Sci 2010 Jan; 23(1): 42–7PubMedGoogle Scholar
  197. 197.
    Asdaq SM, Inamdar MN. The potential benefits of a garlic and hydrochlorothiazide combination as antihypertensive and cardioprotective in rats. J Nat Med 2011 Jan; 65(1): 81–8PubMedCrossRefGoogle Scholar
  198. 198.
    Asdaq SM, Inamdar MN. Pharmacodynamic interaction of garlic with hydrochlorothiazide in rats. Indian J Physiol Pharmacol 2009 Apr-Jun; 53(2): 127–36PubMedGoogle Scholar
  199. 199.
    Asdaq SM, Inamdar MN. The potential for interaction of hydrochlorothiazide with garlic in rats. Chem Biol Interact 2009 Oct 30; 181(3): 472–9PubMedCrossRefGoogle Scholar
  200. 200.
    Asdaq SM, Inamdar MN. Pharmacodynamic interaction of captopril with garlic in isoproterenol-induced myocardial damage in rat. Phytother Res 2010 May; 24(5): 720–5PubMedGoogle Scholar
  201. 201.
    Pedraza-Chaverri J, Yam-Canul P, Chirino YI, et al. Protective effects of garlic powder against potassium dichromate-induced oxidative stress and nephrotoxicity. Food Chem Toxicol 2008 Feb; 46(2): 619–27PubMedCrossRefGoogle Scholar
  202. 202.
    Howard EW, Lee DT, Chiu YT, et al. Evidence of a novel docetaxel sensitizer, garlic-derived S-allylmercaptocysteine, as a treatment option for hormone refractory prostate cancer. Int J Cancer 2008 May; 122(9): 1941–8PubMedCrossRefGoogle Scholar
  203. 203.
    Taghizadeh AA, Shirpoor A, Dodangeh BE. The effect of garlic on cyclosporine-A-induced hyperlipidemia in male rats. Urol J 2005; 2(3): 153–6Google Scholar
  204. 204.
    Durak I, Cetin R, Candir O, et al. Black grape and garlic extracts protect against cyclosporine a nephrotoxicity. Immunol Invest 2007; 36(1): 105–14PubMedCrossRefGoogle Scholar
  205. 205.
    Le Bon AM, Vernevaut MF, Guenot L, et al. Effects of garlic powders with varying alliin contents on hepatic drug metabolizing enzymes in rats. J Agric Food Chem 2003 Dec; 51(26): 7617–23PubMedCrossRefGoogle Scholar
  206. 206.
    Wu CC, Sheen LY, Chen HW, et al. Differential effects of garlic oil and its three major organosulfur components on the hepatic detoxification system in rats. J Agric Food Chem 2002 Jan; 50(2): 378–83PubMedCrossRefGoogle Scholar
  207. 207.
    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 May–Aug; 4(2): 176–84PubMedGoogle Scholar
  208. 208.
    Zou L, Harkey MR, Henderson GL. Effects of herbal components on cDNA-expressed cytochrome P450 enzyme catalytic activity. Life Sci 2002 Aug; 71(13): 1579–89PubMedCrossRefGoogle Scholar
  209. 209.
    Greenblatt DJ, Leigh-Pemberton RA, von Moltke LL. In vitro interactions of water-soluble garlic components with human cytochromes p450. J Nutr 2006 Mar; 136(3 Suppl.): 806S–9SPubMedGoogle Scholar
  210. 210.
    Ho BE, Shen DD, McCune JS, et al. Effects of garlic on cytochromes P450 2C9- and 3A4-mediated drug metabolism in human hepatocytes. Sci Pharm 2010 Oct; 78(3): 473–81PubMedCrossRefGoogle Scholar
  211. 211.
    Fujita K, Kamataki T. Screening of organosulfur compounds as inhibitors of human CYP2A6. Drug Metab Dispos 2001 Jul; 29(7): 983–9PubMedGoogle Scholar
  212. 212.
    Arora A, Seth K, Shukla Y. Reversal of P-glycoprotein-mediated multidrug resistance by diallyl sulfide in K562 leukemic cells and in mouse liver. Carcinogenesis 2004 Jun; 25(6): 941–9PubMedCrossRefGoogle Scholar
  213. 213.
    Nabekura T, Kamiyama S, Kitagawa S. Effects of dietary chemopreventive phytochemicals on P-glycoprotein function. Biochem Biophys Res Commun 2005 Feb; 327(3): 866–70PubMedCrossRefGoogle Scholar
  214. 214.
    Engdal S, Nilsen OG. Inhibition of P-glycoprotein in Caco-2 cells: effects of herbal remedies frequently used by cancer patients. Xenobiotica 2008 Jun; 38(6): 559–73PubMedCrossRefGoogle Scholar
  215. 215.
    Berginc K, Zakelj S, Kristl A. In vitro interactions between aged garlic extract and drugs used for the treatment of cardiovascular and diabetic patients. Eur J Nutr 2010 Sep; 49(6): 373–84PubMedCrossRefGoogle Scholar
  216. 216.
    Berginc K, Zakelj S, Ursic D, et al. Aged garlic extract stimulates P-glycoprotein and multidrug resistance associated protein 2 mediated effluxes. Biol Pharm Bull 2009 Apr; 32(4): 694–9PubMedCrossRefGoogle Scholar
  217. 217.
    Lii CK, Tsai CW, Wu CC. Garlic allyl sulfides display differential modulation of rat cytochrome P450 2B1 and the placental form glutathione S-transferase in various organs. J Agric Food Chem 2006 Jul; 54(14): 5191–6PubMedCrossRefGoogle Scholar
  218. 218.
    Taubert D, Glockner R, Muller D, et al. The garlic ingredient diallyl sulfide inhibits cytochrome P450 2E1 dependent bioactivation of acrylamide to glycidamide. Toxicol Lett 2006 Jun; 164(1): 1–5PubMedCrossRefGoogle Scholar
  219. 219.
    Patel J, Buddha B, Dey S, et al. In vitro interaction of the HIV protease inhibitor ritonavir with herbal constituents: changes in P-gp and CYP3A4 activity. Am J Ther 2004 Jul–Aug; 11(4): 262–77PubMedCrossRefGoogle Scholar
  220. 220.
    Berginc K, Trontelj J, Kristl A. The influence of aged garlic extract on the uptake of saquinavir and darunavir into HepG2 cells and rat liver slices. Drug Metab Pharmacokinet 2010; 25(3): 307–13PubMedCrossRefGoogle Scholar
  221. 221.
    Berginc K, Milisav I, Kristl A. Garlic flavonoids and organosulfur compounds: impact on the hepatic pharmacokinetics of saquinavir and darunavir. Drug Metab Pharmacokinet 2010; 25(6): 521–30PubMedCrossRefGoogle Scholar
  222. 222.
    Berginc K, Trdan T, Trontelj J, et al. HIV protease inhibitors: garlic supplements and first-pass intestinal metabolism impact on the therapeutic efficacy. Biopharm Drug Dispos 2010 Nov; 31(8-9): 495–505PubMedCrossRefGoogle Scholar
  223. 223.
    Saw JT, Bahari MB, Ang HH, et al. Potential drug-herb interaction with antiplatelet/anticoagulant drugs. Complement Ther Clin Pract 2006 Nov; 12(4): 236–41PubMedCrossRefGoogle Scholar
  224. 224.
    Borrelli F, Capasso R, Izzo AA. Garlic (Allium sativum L.): adverse effects and drug interactions in humans. Mol Nutr Food Res 2007 Nov; 51(11): 1386–97PubMedCrossRefGoogle Scholar
  225. 225.
    Weinmann S, Roll S, Schwarzbach C, et al. Effects of Ginkgo biloba in dementia: systematic review and meta-analysis. BMC Geriatr 2010 Mar 17; 10:14PubMedCrossRefGoogle Scholar
  226. 226.
    Haemorrhage due to Ginkgo biloba? Prescrire Int 2008; 17: 19Google Scholar
  227. 227.
    Ryu KH, Han HY, Lee SY, et al. Ginkgo biloba extract enhances antiplatelet and antithrombotic effects of cilostazol without prolongation of bleeding time. Thromb Res 2009 Jul; 124(3): 328–34PubMedCrossRefGoogle Scholar
  228. 228.
    Gardner CD, Zehnder JL, Rigby AJ, et al. Effect of Ginkgo biloba (EGb 761) and aspirin on platelet aggregation and platelet function analysis among older adults at risk of cardiovascular disease: a randomized clinical trial. Blood Coagul Fibrinolysis 2007 Dec; 18(8): 787–93PubMedCrossRefGoogle Scholar
  229. 229.
    Wolf HR. Does Ginkgo biloba special extract EGb 761 provide additional effects on coagulation and bleeding when added to acetylsalicylic acid 500mg daily? Drugs R D 2006; 7(3): 163–72PubMedCrossRefGoogle Scholar
  230. 230.
    Bone KM. Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what is the evidence? Mol Nutr Food Res 2008 Jul; 52(7): 764–71PubMedCrossRefGoogle Scholar
  231. 231.
    Gaudineau C, Beckerman R, Welbourn S, et al. Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract. Biochem Biophys Res Commun 2004 Jun; 318(4): 1072–8PubMedCrossRefGoogle Scholar
  232. 232.
    Deng Y, Bi HC, Zhao LZ, et al. Induction of cytochrome P450 3A by the Ginkgo biloba extract and bilobalides in human and rat primary hepatocytes. Drug Metab Lett 2008 Jan; 2(1): 60–6PubMedCrossRefGoogle Scholar
  233. 233.
    Etheridge AS, Black SR, Patel PR, et al. An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constituents. Planta Med 2007 Jul; 73(8): 731–41PubMedCrossRefGoogle Scholar
  234. 234.
    Chang TK, Chen J, Yeung EY. Effect of Ginkgo biloba extract on procarcinogen-bioactivating human CYP1 enzymes: identification of isorhamnetin, kaempferol, and quercetin as potent inhibitors of CYP1B1. Toxicol Appl Pharmacol 2006 May; 213(1): 18–26PubMedCrossRefGoogle Scholar
  235. 235.
    von Moltke LL, Weemhoff JL, Bedir E, et al. Inhibition of human cytochromes P450 by components of Ginkgo biloba. J Pharm Pharmacol 2004 Aug; 56(8): 1039–44CrossRefGoogle Scholar
  236. 236.
    Ribonnet L, Callebaut A, Nobels I, et al. Modulation of CYP1A1 activity by a Ginkgo biloba extract in the human intestinal Caco-2 cells. Toxicol Lett 2011 May; 202(3): 193–202PubMedCrossRefGoogle Scholar
  237. 237.
    Rajaraman G, Yang G, Chen J, et al. Modulation of CYP1B1 and CYP1A1 gene expression and activation of aryl hydrocarbon receptor by Ginkgo biloba extract in MCF-10A human mammary epithelial cells. Can J Physiol Pharmacol 2009 Sep; 87(9): 674–83PubMedCrossRefGoogle Scholar
  238. 238.
    Wang Y, Cao J, Zeng S. Involvement of P-glycoprotein in regulating cellular levels of Ginkgo flavonols: quercetin, kaempferol, and isorhamnetin. J Pharm Pharmacol 2005 Jun; 57(6): 751–8PubMedCrossRefGoogle Scholar
  239. 239.
    Deng Y, Bi HC, Zhao LZ, et al. Induction of cytochrome P450s by terpene trilactones and flavonoids of the Ginkgo biloba extract EGb 761 in rats. Xenobiotica 2008 May; 38(5): 465–81PubMedCrossRefGoogle Scholar
  240. 240.
    Umegaki K, Saito K, Kubota Y, et al. Ginkgo biloba extract markedly induces pentoxyresorufin O-dealkylase activity in rats. Jpn J Pharmacol 2002 Dec; 90(4): 345–51PubMedCrossRefGoogle Scholar
  241. 241.
    Sugiyama T, Kubota Y, Shinozuka K, et al. Induction and recovery of hepatic drug metabolizing enzymes in rats treated with Ginkgo biloba extract. Food Chem Toxicol 2004 Jun; 42(6): 953–7PubMedCrossRefGoogle Scholar
  242. 242.
    Tada Y, Kagota S, Kubota Y, et al. Long-term feeding of Ginkgo biloba extract impairs peripheral circulation and hepatic function in aged spontaneously hypertensive rats. Biol Pharm Bull 2008 Jan; 31(1): 68–72PubMedCrossRefGoogle Scholar
  243. 243.
    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 Jul; 75(9): 1113–22PubMedCrossRefGoogle Scholar
  244. 244.
    Kubota Y, Kobayashi K, Tanaka N, et al. Pretreatment with Ginkgo biloba extract weakens the hypnosis action of phenobarbital and its plasma concentration in rats. J Pharm Pharmacol 2004 Mar; 56(3): 401–5PubMedCrossRefGoogle Scholar
  245. 245.
    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 Apr; 70(23): 2783–92PubMedCrossRefGoogle Scholar
  246. 246.
    Kubota Y, Kobayashi K, Tanaka N, et al. Interaction of Ginkgo biloba extract (GBE) with hypotensive agent, nicardipine, in rats. In Vivo 2003 Sep–Oct; 17(5): 409–12PubMedGoogle Scholar
  247. 247.
    Yoshioka M, Ohnishi N, Sone N, et al. Studies on interactions between functional foods or dietary supplements and medicines: III. Effects of Ginkgo biloba leaf extract on the pharmacokinetics of nifedipine in rats. Biol Pharm Bull 2004 Dec; 27(12): 2042–5PubMedCrossRefGoogle Scholar
  248. 248.
    Yang CY, Chao PD, Hou YC, et al. Marked decrease of cyclosporin bioavailability caused by coadministration of Ginkgo and onion in rats. Food Chem Toxicol 2006 Sep; 44(9): 1572–8PubMedCrossRefGoogle Scholar
  249. 249.
    Zhao LZ, Huang M, Chen J, et al. Induction of propranolol metabolism by Ginkgo biloba extract EGb 761 in rats. Curr Drug Metab 2006 Aug; 7(6): 577–87PubMedCrossRefGoogle Scholar
  250. 250.
    Tang J, Sun J, Zhang Y, et al. Herb-drug interactions: effect of Ginkgo biloba extract on the pharmacokinetics of theophylline in rats. Food Chem Toxicol 2007 Dec; 45(12): 2441–5PubMedCrossRefGoogle Scholar
  251. 251.
    Ettefagh KA, Burns JT, Junio HA, et al. Goldenseal (Hydrastis canadensis L.) extracts synergistically enhance the antibacterial activity of berberine via efflux pump inhibition. Planta Med 2011 May; 77(8): 835–40PubMedCrossRefGoogle Scholar
  252. 252.
    Douglas JA, Follett JM, Parmenter GA, et al. Seasonal variation of biomass and bioactive alkaloid content of goldenseal, Hydrastis canadensis. Fitoterapia 2010 Oct; 81(7): 925–8PubMedCrossRefGoogle Scholar
  253. 253.
    Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003 May; 10(4): 334–42PubMedCrossRefGoogle Scholar
  254. 254.
    Chatterjee P, Franklin MR. Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos 2003 Nov; 31(11): 1391–7PubMedCrossRefGoogle Scholar
  255. 255.
    Budzinski JW, Trudeau VL, Drouin CE, et al. Modulation of human cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal products. Can J Physiol Pharmacol 2007 Sep; 85(9): 966–78PubMedCrossRefGoogle Scholar
  256. 256.
    Qiu W, Jiang XH, Liu CX, et al. Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-gp. Phytother Res 2009 Nov; 23(11): 1553–8PubMedCrossRefGoogle Scholar
  257. 257.
    Sarris J, LaPorte E, Schweitzer I. Kava: a comprehensive review of efficacy, safety, and psychopharmacology. Aust N Z J Psychiatry 2011 Jan; 45(1): 27–35PubMedCrossRefGoogle Scholar
  258. 258.
    Teschke R, Qiu SX, Lebot V. Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culprits. Dig Liver Dis 2011 Sep; 43(9): 676–813PubMedCrossRefGoogle Scholar
  259. 259.
    Sarris J, Teschke R, Stough C, et al. Re-introduction of kava (Piper methysticum) to the EU: is there a way forward? Planta Med 2011 Jan; 77(2): 107–10PubMedCrossRefGoogle Scholar
  260. 260.
    Teschke R, Schulze J. Risk of kava hepatotoxicity and the FDA consumer advisory. JAMA 2010 Nov; 304(19): 2174–5PubMedCrossRefGoogle Scholar
  261. 261.
    Almeida JC, Grimsley EW. Coma from the health food store: interaction between kava and alprazolam. Ann Intern Med 1996 Dec; 125(11): 940–1PubMedGoogle Scholar
  262. 262.
    Mathews JM, Etheridge AS, Black SR. Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab Dispos 2002 Nov; 30(11): 1153–7PubMedCrossRefGoogle Scholar
  263. 263.
    Zou L, Henderson GL, Harkey MR, et al. Effects of kava (kava-kava, ‘awa, yaqona, Piper methysticum) on c-DNA-expressed cytochrome P450 enzymes and human cryopreserved hepatocytes. Phytomedicine 2004; 11(4): 285–94PubMedCrossRefGoogle Scholar
  264. 264.
    Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004; 18(19): 2273–81PubMedCrossRefGoogle Scholar
  265. 265.
    Unger M, Holzgrabe U, Jacobsen W, et al. Inhibition of cytochrome P450 3A4 by extracts and kavalactones of Piper methysticum (kava-kava). Planta Med 2002 Dec; 68(12): 1055–8PubMedCrossRefGoogle Scholar
  266. 266.
    Yueh MF, Kawahara M, Raucy J. High volume bioassays to assess CYP3A4-mediated drug interactions: induction and inhibition in a single cell line. Drug Metab Dispos 2005 Jan; 33(1): 38–48PubMedCrossRefGoogle Scholar
  267. 267.
    Weiss J, Sauer A, Frank A, et al. Extracts and kavalactones of Piper methysticum G. Forst (kava-kava) inhibit P-glycoprotein in vitro. Drug Metab Dispos 2005 Nov; 33(11): 1580–3PubMedCrossRefGoogle Scholar
  268. 268.
    Lim ST, Dragull K, Tang CS, et al. Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats. Toxicol Sci 2007 May; 97(1): 214–21PubMedCrossRefGoogle Scholar
  269. 269.
    Yamazaki Y, Hashida H, Arita A, et al. High dose of commercial products of kava (Piper methysticum) markedly enhanced hepatic cytochrome P450 1A1 mRNA expression with liver enlargement in rats. Food Chem Toxicol 2008 Dec; 46(12): 3732–8PubMedCrossRefGoogle Scholar
  270. 270.
    Mathews JM, Etheridge AS, Valentine JL, et al. Pharmacokinetics and disposition of the kavalactone kawain: interaction with kava extract and kavalactones in vivo and in vitro. Drug Metab Dispos 2005 Oct; 33(10): 1555–63PubMedCrossRefGoogle Scholar
  271. 271.
    Russmann S, Lauterburg BH, Barguil Y, et al. Traditional aqueous kava extracts inhibit cytochrome P450 1A2 in humans: protective effect against environmental carcinogens? Clin Pharmacol Ther 2005 May; 77(5): 453–4PubMedCrossRefGoogle Scholar
  272. 272.
    Abenavoli L, Capasso R, Milic N, et al. Milk thistle in liver diseases: past, present, future. Phytother Res 2010 Oct; 24(10): 1423–32PubMedCrossRefGoogle Scholar
  273. 273.
    Maghrani M, Zeggwagh NA, Lemhadri A, et al. Study of the hypoglycaemic activity of Fraxinus excelsior and Silybum marianum in an animal model of type 1 diabetes mellitus. J Ethnopharmacol 2004 Apr; 91(2–3): 309–16PubMedCrossRefGoogle Scholar
  274. 274.
    Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother Res 2006 Dec; 20(12): 1036–9PubMedCrossRefGoogle Scholar
  275. 275.
    Zuber R, Modrianský M, Dvorák Z, et al. Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities. Phytother Res 2002 Nov; 16(7): 632–8PubMedCrossRefGoogle Scholar
  276. 276.
    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 Nov; 28(11): 1270–3PubMedGoogle Scholar
  277. 277.
    Sridar C, Goosen TC, Kent UM, et al. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 2004 Jun; 32(6): 587–94PubMedCrossRefGoogle Scholar
  278. 278.
    Brantley SJ, Oberlies NH, Kroll DJ, et al. Two flavonolignans from milk thistle (Silybum marianum) inhibit CYP2C9-mediated warfarin metabolism at clinically achievable concentrations. J Pharmacol Exp Ther 2010 Mar; 332(3): 1081–7PubMedCrossRefGoogle Scholar
  279. 279.
    Wu JW, Lin LC, Tsai TH. Drug-drug interactions of silymarin on the perspective of pharmacokinetics. J Ethnopharmacol 2009 Jan 21; 121(2): 185–93PubMedCrossRefGoogle Scholar
  280. 280.
    Kosina P, Maurel P, Ulrichová J, et al. Effect of silybin and its glycosides on the expression of cytochromes P450 1A2 and 3A4 in primary cultures of human hepatocytes. J Biochem Mol Toxicol 2005; 19(3): 149–53PubMedCrossRefGoogle Scholar
  281. 281.
    Doehmer J, Tewes B, Klein KU, et al. Assessment of drug-drug interaction for silymarin. Toxicol In Vitro 2008 Apr; 22(3): 610–7PubMedCrossRefGoogle Scholar
  282. 282.
    Doehmer J, Weiss G, McGregor GP, et al. Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome-P450 activities. Toxicol In Vitro 2011 Feb; 25(1): 21–7PubMedCrossRefGoogle Scholar
  283. 283.
    Kang MK, Bae SK, Kim JW, et al. Pharmacokinetic interaction between oltipraz and silymarin in rats. J Pharm Pharm Sci 2009; 12(1): 1–16PubMedGoogle Scholar
  284. 284.
    Chang JC, Wu YT, Lee WC, et al. Herb-drug interaction of silymarin or silibinin on the pharmacokinetics of trazodone in rats. Chem Biol Interact 2009 Dec; 182(2-3): 227–32PubMedCrossRefGoogle Scholar
  285. 285.
    Qi LW, Wang CZ, Yuan CS. Isolation and analysis of ginseng: advances and challenges. Nat Prod Rep 2011 Mar; 28(3): 467–95PubMedCrossRefGoogle Scholar
  286. 286.
    Summaries for patients: ginseng reduces the effect of warfarin in a study of healthy volunteers. Ann Intern Med 2004; 141:I58Google Scholar
  287. 287.
    Janetzky K, Morreale AP. Probable interaction between warfarin and ginseng. Am J Health Syst Pharm 1997 Mar; 54(6): 692–3PubMedGoogle Scholar
  288. 288.
    Bilgi N, Bell K, Ananthakrishnan AN, et al. Imatinib and Panax ginseng: a potential interaction resulting in liver toxicity. Ann Pharmacother 2010 May; 44(5): 926–8PubMedCrossRefGoogle Scholar
  289. 289.
    Foster BC, Vandenhoek S, Tang R, et al. Effect of several Chinese natural health products of human cytochrome P450 metabolism. J Pharm Pharm Sci 2002 May-Aug; 5(2): 185–9PubMedGoogle Scholar
  290. 290.
    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
  291. 291.
    He N, Xie HG, Collins X, et al. Effects of individual ginsenosides, ginkgolides and flavonoids on CYP2C19 and CYP2D6 activity in human liver micro-somes. Clin Exp Pharmacol Physiol 2006 Sep; 33(9): 813–5PubMedCrossRefGoogle Scholar
  292. 292.
    Chang TK, 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 Apr; 30(4): 378–84PubMedCrossRefGoogle Scholar
  293. 293.
    Liu Y, Zhang JW, Li W, et al. Ginsenoside metabolites, rather than naturally occurring ginsenosides, lead to inhibition of human cytochrome P450 enzymes. Toxicol Sci 2006 Jun; 91(2): 356–64PubMedCrossRefGoogle Scholar
  294. 294.
    Hao M, Zhao Y, Chen P, et al. Structure-activity relationship and substrate-dependent phenomena in effects of ginsenosides on activities of drug-metabolizing P450 enzymes. PLoS One 2008 Jul 16; 3(7): e2697PubMedCrossRefGoogle Scholar
  295. 295.
    Yu CT, Chen J, Teng XW, et al. Lack of evidence for induction of CYP2B1, CYP3A23, and CYP1A2 gene expression by Panax ginseng and Panax quinquefolius extracts in adult rats and primary cultures of rat hepatocytes. Drug Metab Dispos 2005 Jan; 33(1): 19–22PubMedCrossRefGoogle Scholar
  296. 296.
    Zhang R, Jie J, Zhou Y, et al. Long-term effects of Panax ginseng on disposition of fexofenadine in rats in vivo. Am J Chin Med 2009; 37(4): 657–67PubMedCrossRefGoogle Scholar
  297. 297.
    Yuan CS, Wang CZ, Wicks SM, et al. Chemical and pharmacological studies of saponins with a focus on American ginseng. J Ginseng Res 2010 Sep; 34(3): 160–7PubMedCrossRefGoogle Scholar
  298. 298.
    Qi LW, Wang CZ, Yuan CS. Ginsenosides from American ginseng: chemical and pharmacological diversity. Phytochemistry 2011 Jun; 72(8): 689–99PubMedCrossRefGoogle Scholar
  299. 299.
    Scholey A, Ossoukhova A, Owen L, et al. Effects of American ginseng (Panax quinquefolius) on neurocognitive function: an acute, randomised, double-blind, placebo-controlled, crossover study. Psychopharmacology (Berl) 2010 Oct; 212(3): 345–56CrossRefGoogle Scholar
  300. 300.
    Sinescu I, Geavlete P, Multescu R, et al. Long-term efficacy of serenoa repens treatment in patients with mild and moderate symptomatic benign prostatic hyperplasia. Urol Int 2011; 86(3): 284–9PubMedCrossRefGoogle Scholar
  301. 301.
    Agbabiaka TB, Pittler MH, Wider B, et al. Serenoa repens (saw palmetto): a systematic review of adverse events. Drug Saf 2009; 32(8): 637–47PubMedCrossRefGoogle Scholar
  302. 302.
    Solomon D, Ford E, Adams J, et al. Potential of St John’s wort for the treatment of depression: the economic perspective. Aust N Z J Psychiatry 2011 Feb;45(2): 123–30PubMedCrossRefGoogle Scholar
  303. 303.
    Shelton RC. St John’s wort (Hypericum perforatum) in major depression. J Clin Psychiatry 2009; 70 Suppl. 5: 23–7CrossRefGoogle Scholar
  304. 304.
    Butterweck V, Schmidt M. St John’s wort: role of active compounds for its mechanism of action and efficacy. Wien Med Wochenschr 2007; 157(13–14): 356–61PubMedCrossRefGoogle Scholar
  305. 305.
    Madabushi R, Frank B, Drewelow B, et al. Hyperforin in St John’s wort drug interactions. Eur J Clin Pharmacol 2006 Mar; 62(3): 225–33PubMedCrossRefGoogle Scholar
  306. 306.
    Di YM, Li CG, Xue CC, et al. Clinical drugs that interact with St John’s wort and implication in drug development. Curr Pharm Des 2008; 14(17): 1723–42PubMedCrossRefGoogle Scholar
  307. 307.
    Zhou SF, Lai X. An update on clinical drug interactions with the herbal antidepressant St John’s wort. Curr Drug Metab 2008 Jun; 9(5): 394–409PubMedCrossRefGoogle Scholar
  308. 308.
    Borrelli F, Izzo AA. Herb-drug interactions with St John’s wort (Hypericum perforatum): an update on clinical observations. AAPS J 2009 Dec; 11(4): 710–27PubMedCrossRefGoogle Scholar
  309. 309.
    Vlachojannis J, Cameron M, Chrubasik S. Drug interactions with St John’s wort products. Pharmacol Res 2011 Mar; 63(3): 254–6PubMedCrossRefGoogle Scholar
  310. 310.
    Sherman C. Herbal use may affect psychotropic response: serotonin syndrome has been reported in patients who use both St John’s wort and an SSRI. Clin Psychiatry News 2006 Nov 1 [online]. Available from URL: http://www.clinicalpsychiatrynews.com/news/more-top-news/single-view/herbal-use-may-affect-psychotropic-response-serotonin-syndrome-has-been-reported-in-patients-who-used-both-st-john-s-wort-and-an-ssri/7a3280d7bf.html [Accessed 2011 Nov 18]
  311. 311.
    Lau WC, Welch TD, Shields T, et al. The effect of St John’s wort on the pharmacodynamic response of clopidogrel in hyporesponsive volunteers and patients: increased platelet inhibition by enhancement of CYP3A4 metabolic activity. J Cardiovasc Pharmacol 2011 Jan; 57(1): 86–93PubMedCrossRefGoogle Scholar
  312. 312.
    Schwarz D, Kisselev P, Roots I. St John’s wort extracts and some of their constituents potently inhibit ultimate carcinogen formation from benzo[a]pyrene-7,8-dihydrodiol by human CYP1A1. Cancer Res 2003 Nov; 63(22): 8062–8PubMedGoogle Scholar
  313. 313.
    Chaudhary A, Willett KL. Inhibition of human cytochrome CYP 1 enzymes by flavonoids of St John’s wort. Toxicology 2006 Jan; 217(2-3): 194–205PubMedCrossRefGoogle Scholar
  314. 314.
    Gödtel-Armbrust U, Metzger A, Kroll U, et al. Variability in PXR-mediated induction of CYP3A4 by commercial preparations and dry extracts of St John’s wort. Naunyn Schmiedebergs Arch Pharmacol 2007 Aug; 375(6): 377–82PubMedCrossRefGoogle Scholar
  315. 315.
    Komoroski BJ, Zhang S, Cai H, et al. Induction and inhibition of cytochromes P450 by the St John’s wort constituent hyperforin in human hepatocyte cultures. Drug Metab Dispos 2004 May; 32(5): 512–8PubMedCrossRefGoogle Scholar
  316. 316.
    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 Jun; 97(13): 7500–2PubMedCrossRefGoogle Scholar
  317. 317.
    Kober M, Pohl K, Efferth T. Molecular mechanisms underlying St John’s wort drug interactions. Curr Drug Metab 2008 Dec; 9(10): 1027–37PubMedCrossRefGoogle Scholar
  318. 318.
    Liu YH, Mo SL, Bi HC, et al. Regulation of human pregnane X receptor and its target gene cytochrome P450 3A4 by Chinese herbal compounds and a molecular docking study. Xenobiotica 2011 Apr; 41(4): 259–80PubMedCrossRefGoogle Scholar
  319. 319.
    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 Mar; 66(1): 27–33PubMedCrossRefGoogle Scholar
  320. 320.
    Bray BJ, Brennan NJ, Perry NB, et al. Short term treatment with St John’s wort, hypericin or hyperforin fails to induce CYP450 isoforms in the Swiss Webster mouse. Life Sci 2002 Feb; 70(11): 1325–35PubMedCrossRefGoogle Scholar
  321. 321.
    Cantoni L, Rozio M, Mangolini A, et al. Hyperforin contributes to the hepatic CYP3A-inducing effect of Hypericum perforatum extract in the mouse. Toxicol Sci 2003 Sep; 75(1): 25–30PubMedCrossRefGoogle Scholar
  322. 322.
    Ho YF, Huang DK, Hsueh WC, et al. Effects of St John’s wort extract on indinavir pharmacokinetics in rats: differentiation of intestinal and hepatic impacts. Life Sci 2009 Aug 12; 85(7-8): 296–302PubMedCrossRefGoogle Scholar
  323. 323.
    Dostalek M, Pistovcakova J, Jurica J, et al. Effect of St John’s wort (Hypericum perforatum) on cytochrome P-450 activity in perfused rat liver. Life Sci 2005 Dec; 78(3): 239–44PubMedCrossRefGoogle Scholar
  324. 324.
    Shibayama Y, Ikeda R, Motoya T, et al. St John’s wort (Hypericum perforatum) induces overexpression of multidrug resistance protein 2 (MRP2) in rats: a 30-day ingestion study. Food Chem Toxicol 2004 Jun; 42(6): 995–1002PubMedCrossRefGoogle Scholar
  325. 325.
    Garrovo C, Rosati A, Bartoli F, et al. St John’s wort modulation and developmental expression of multidrug transporters in the rat. Phytother Res 2006 Jun; 20(6): 468–73PubMedCrossRefGoogle Scholar
  326. 326.
    Perloff MD, von Moltke LL, Störmer E, et al. Saint John’s wort: an in vitro analysis of P-glycoprotein induction due to extended exposure. Br J Pharmacol 2001 Dec; 134(8): 1601–8PubMedCrossRefGoogle Scholar
  327. 327.
    Tian R, Koyabu N, Morimoto S, et al. Functional induction and de-induction of P-glycoprotein by St John’s wort and its ingredients in a human colon adenocarcinoma cell line. Drug Metab Dispos 2005 Apr; 33(4): 547–54PubMedCrossRefGoogle Scholar
  328. 328.
    Weber CC, Kressmann S, Fricker G, et al. Modulation of P-glycoprotein function by St John’s wort extract and its major constituents. Pharma-copsychiatry 2004 Nov; 37(6): 292–8CrossRefGoogle Scholar
  329. 329.
    Gutmann H, Poller B, Büter KB, et al. Hypericum perforatum: which constituents may induce intestinal MDR1 and CYP3A4 mRNA expression? Planta Med 2006 Jun; 72(8): 685–90PubMedCrossRefGoogle Scholar
  330. 330.
    Wang EJ, Barecki-Roach M, Johnson WW. Quantitative characterization of direct P-glycoprotein inhibition by St John’s wort constituents hypericin and hyperforin. J Pharm Pharmacol 2004 Jan; 56(1): 123–8PubMedCrossRefGoogle Scholar
  331. 331.
    Ott M, Huls M, Cornelius MG, et al. St John’s wort constituents modulate P-glycoprotein transport activity at the blood-brain barrier. Pharm Res 2010 May; 27(5): 811–22PubMedCrossRefGoogle Scholar
  332. 332.
    Nowack R. Review article: cytochrome P450 enzyme, and transport protein mediated herb-drug interactions in renal transplant patients: grapefruit juice, St John’s wort — and beyond! Nephrology (Carlton) 2008 Jun; 13(4): 337–47CrossRefGoogle Scholar
  333. 333.
    Whitten DL, Myers SP, Hawrelak JA, et al. The effect of St John’s wort extracts on CYP3A: a systematic review of prospective clinical trials. Br J Clin Pharmacol 2006 Nov; 62(5): 512–26PubMedCrossRefGoogle Scholar
  334. 334.
    Markowitz JS, von Moltke LL, Donovan JL. Predicting interactions between conventional medications and botanical products on the basis of in vitro investigations. Mol Nutr Food Res 2008 Jul; 52(7): 747–54PubMedCrossRefGoogle Scholar
  335. 335.
    Venkataramanan R, Komoroski B, Strom S. In vitro and in vivo assessment of herb drug interactions. Life Sci 2006 Mar; 78(18): 2105–15PubMedCrossRefGoogle Scholar
  336. 336.
    Directive 2004/24/EC of the European Parliament and of the Council of 31 March 2004 amending, as regards traditional herbal medicinal products, Directive 2001/83/EC on the Community code relating to medicinal products for human use. Official Journal of the European Union 2004 Apr 30 [online]. Available from URL: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2004:136:0085:0090:en:PDF [Accessed 2011 Nov 18]
  337. 337.
    Shi S, Mörike K, Klotz U. The clinical implications of ageing for rational drug therapy. Eur J Clin Pharmacol 2008 Feb; 64(2): 183–99PubMedCrossRefGoogle Scholar
  338. 338.
    Klotz U. The elderly: a challenge for appropriate drug treatment. Eur J Clin Pharmacol 2008 Mar; 64(3): 225–6PubMedCrossRefGoogle Scholar
  339. 339.
    Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev 2009; 41(2): 67–76PubMedCrossRefGoogle Scholar
  340. 340.
    Shi S, Klotz U. Age-related changes in pharmacokinetics. Curr Drug Metab Epub 2011 Apr 18Google Scholar

Copyright information

© Adis Data Information BV 2012

Authors and Affiliations

  1. 1.Department of Pharmacy, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanP.R. China
  2. 2.Dr Margarete Fischer-Bosch Institute of Clinical PharmacologyStuttgartGermany
  3. 3.University of TuebingenTuebingenGermany

Personalised recommendations