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Drugs

, Volume 70, Issue 18, pp 2373–2407 | Cite as

Grapefruit-Drug Interactions

  • Kay Seden
  • Laura Dickinson
  • Saye Khoo
  • David Back
Review Article

Abstract

Grapefruit juice and grapefruit product consumption have potential health benefits; however, their intake is also associated with interactions with certain drugs, including calcium channel blockers, immunosuppressants and antihistamines. The primary mechanism through which interactions are mediated is mechanism-based intestinal cytochrome P450 3A4 inhibition by furanocoumarins resulting in increased bioavailability of administered medications that are substrates. Grapefruit products have also been associated with interactions with P-glycoprotein (P-gp) and uptake transporters (e.g. organic anion-transporting polypeptides [OATPs]). Polyphenolic compounds such as flavonoids have been proposed as the causative agents of the P-gp and OATP interactions. The mechanisms and magnitudes of the interactions can be influenced by the concentrations of furanocoumarins and flavonoids in the grapefruit product, the volume of juice consumed, and the inherent variability of specific enzymes and transporter components in humans. It is therefore challenging to predict the extent of grapefruit product-drug interactions and to compare available in vitro and in vivo data. The clinical significance of such interactions also depends on the disposition and toxicity profile of the drug being administered. The aim of this review is to outline the mechanisms of grapefruit-drug interactions and present a comprehensive summary of those agents affected and whether they are likely to be of clinical relevance.

Keywords

Felodipine Aliskiren Cilostazol Grapefruit Juice Naringin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors thank the National Institute of Health Research (NIHR-Department of Health) and the Northwest Development Agency (NWDA) for infrastructural and project support.

Transparency declaration: This review was in part funded by the Florida Department of Citrus (FDOC).

Supplementary material

40265_2012_70182373_MOESM1_ESM.pdf (281 kb)
Supplementary material, approximately 288 KB.

References

  1. 1.
    Mertens-Talcott SU, Zadezensky I, De Castro WV, et al. Grapefruit-drug interactions: can interactions with drugs be avoided? J Clin Pharmacol 2006 Dec; 46(12): 1390–416PubMedCrossRefGoogle Scholar
  2. 2.
    Gmitter Jr FG. Origin, evolution and breeding of the grapefruit. Plant Breed Rev 1995; 13: 345–63Google Scholar
  3. 3.
    Nicolosi E, Deng ZN, Gentile A, et al. Citrus phylogeny and genetic origin of important species as investigated by molecular markers. Theor Appl Genet 2000; 100(8): 1155–66CrossRefGoogle Scholar
  4. 4.
    Moore GA. Oranges and lemons: clues to the taxonomy of Citrus from molecular markers. Trends Genet 2001 Sep; 17(9): 536–40PubMedCrossRefGoogle Scholar
  5. 5.
    Bailey DG, Spence JD, Edgar B, et al. Ethanol enhances the hemodynamic effects of felodipine. Clin Invest Med 1989 Dec; 12(6): 357–62PubMedGoogle Scholar
  6. 6.
    Bailey DG, Dresser GK. Interactions between grapefruit juice and cardiovascular drugs. Am J Cardiovasc Drugs 2004; 4(5): 281–97PubMedCrossRefGoogle Scholar
  7. 7.
    Neuvonen PJ, Backman JT, Niemi M. Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin. Clin Pharmacokinet 2008; 47(7): 463–74PubMedCrossRefGoogle Scholar
  8. 8.
    Sica DA. Interaction of grapefruit juice and calcium channel blockers. Am J Hypertens 2006 Jul; 19(7): 768–73PubMedCrossRefGoogle Scholar
  9. 9.
    Hukkinen SK, Varhe A, Olkkola KT, et al. Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice. Clin Pharmacol Ther 1995 Aug; 58(2): 127–31PubMedCrossRefGoogle Scholar
  10. 10.
    Kupferschmidt HH, Ha HR, Ziegler WH, et al. Interaction between grapefruit juice and midazolam in humans. Clin Pharmacol Ther 1995 Jul; 58(1): 20–8PubMedCrossRefGoogle Scholar
  11. 11.
    Ozdemir M, Aktan Y, Boydag BS, et al. Interaction between grapefruit juice and diazepam in humans. Eur J Drug Metab Pharmacokinet 1998 Jan-Mar; 23(1): 55–9PubMedCrossRefGoogle Scholar
  12. 12.
    Benton RE, Honig PK, Zamani K, et al. Grapefruit juice alters terfenadine pharmacokinetics, resulting in prolongation of repolarization on the electrocardiogram. Clin Pharmacol Ther 1996 Apr; 59(4): 383–8PubMedCrossRefGoogle Scholar
  13. 13.
    Clifford CP, Adams DA, Murray S, et al. The cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice. Eur J Clin Pharmacol 1997; 52(4): 311–5PubMedCrossRefGoogle Scholar
  14. 14.
    Honig PK, Wortham DC, Lazarev A, et al. Grapefruit juice alters the systemic bioavailability and cardiac repolarization of terfenadine in poor metabolizers of terfenadine. J Clin Pharmacol 1996 Apr; 36(4): 345–51PubMedGoogle Scholar
  15. 15.
    Rau SE, Bend JR, Arnold MO, et al. Grapefruit juiceterfenadine single-dose interaction: magnitude, mechanism, and relevance. Clin Pharmacol Ther 1997 Apr; 61(4): 401–9PubMedCrossRefGoogle Scholar
  16. 16.
    Ducharme MP, Warbasse LH, Edwards DJ. Disposition of intravenous and oral cyclosporine after administration with grapefruit juice. Clin Pharmacol Ther 1995 May; 57(5): 485–91PubMedCrossRefGoogle Scholar
  17. 17.
    Hollander AA, van Rooij J, Lentjes GW, et al. The effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients. Clin Pharmacol Ther 1995 Mar; 57(3): 318–24PubMedCrossRefGoogle Scholar
  18. 18.
    Min DI, Ku YM, Perry PJ, et al. Effect of grapefruit juice on cyclosporine pharmacokinetics in renal transplant patients. Transplantation 1996 Jul 15; 62(1): 123–5PubMedCrossRefGoogle Scholar
  19. 19.
    Yee GC, Stanley DL, Pessa LJ, et al. Effect of grapefruit juice on blood cyclosporin concentration. Lancet 1995 Apr 15; 345(8955): 955–6PubMedCrossRefGoogle Scholar
  20. 20.
    Goosen TC, Cillie D, Bailey DG, et al. Bergamottin contribution to the grapefruit juice-felodipine interaction and disposition in humans. Clin Pharmacol Ther 2004 Dec; 76(6): 607–17PubMedCrossRefGoogle Scholar
  21. 21.
    He K, Iyer KR, Hayes RN, et al. Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice. Chem Res Toxicol 1998 Apr; 11(4): 252–9PubMedCrossRefGoogle Scholar
  22. 22.
    Edwards DJ, Bellevue 3rd FH, Woster PM. Identification of 60,70-dihydroxybergamottin, a cytochrome P450 inhibitor, in grapefruit juice. Drug Metab Dispos 1996 Dec; 24(12): 1287–90PubMedGoogle Scholar
  23. 23.
    Schmiedlin-Ren P, Edwards DJ, Fitzsimmons ME, et al. Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents: decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins. Drug Metab Dispos 1997 Nov;25(11): 1228–33PubMedGoogle Scholar
  24. 24.
    Fukuda K, Ohta T, Oshima Y, et al. Specific CYP3A4 inhibitors in grapefruit juice: furocoumarin dimers as components of drug interaction. Pharmacogenetics 1997 Oct; 7(5): 391–6PubMedCrossRefGoogle Scholar
  25. 25.
    Guo LQ, Fukuda K, Ohta T, et al. Role of furanocoumarin derivatives on grapefruit juice-mediated inhibition of human CYP3A activity. Drug Metab Dispos 2000 Jul; 28(7): 766–71PubMedGoogle Scholar
  26. 26.
    Lilja JJ, Kivisto KT, Backman JT, et al. Effect of grapefruit juice dose on grapefruit juice-triazolam interaction: repeated consumption prolongs triazolam half-life. Eur J Clin Pharmacol 2000 Aug; 56(5): 411–5PubMedCrossRefGoogle Scholar
  27. 27.
    Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin Pharmacol Ther 1999 Aug; 66(2): 118–27PubMedGoogle Scholar
  28. 28.
    Nieminen TH, Hagelberg NM, Saari TI, et al. Grapefruit juice enhances the exposure to oral oxycodone. Basic Clin Pharmacol Toxicol 2010 Oct; 107(4): 782–8PubMedCrossRefGoogle Scholar
  29. 29.
    Bailey DG, Spence JD, Munoz C, et al. Interaction of citrus juices with felodipine and nifedipine. Lancet 1991 Feb 2; 337(8736): 268–9PubMedCrossRefGoogle Scholar
  30. 30.
    Lundahl J, Regardh CG, Edgar B, et al. Effects of grapefruit juice ingestion — pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men. Eur J Clin Pharmacol 1997; 52(2): 139–45PubMedCrossRefGoogle Scholar
  31. 31.
    Lown KS, Bailey DG, Fontana RJ, et al. Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. J Clin Invest 1997 May 15; 99(10): 2545–53PubMedCrossRefGoogle Scholar
  32. 32.
    Lundahl J, Regardh CG, Edgar B, et al. Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects. Eur J Clin Pharmacol 1995; 49(1–2): 61–7PubMedGoogle Scholar
  33. 33.
    Lin JH, Lu AY. Interindividual variability in inhibition and induction of cytochrome P450 enzymes. Annu Rev Pharmacol Toxicol 2001; 41: 535–67PubMedCrossRefGoogle Scholar
  34. 34.
    Paine MF, Khalighi M, Fisher JM, et al. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J Pharmacol Exp Ther 1997 Dec; 283(3): 1552–62PubMedGoogle Scholar
  35. 35.
    Bailey DG, Arnold JM, Munoz C, et al. Grapefruit juice-felodipine interaction: mechanism, predictability, and effect of naringin. Clin Pharmacol Ther 1993 Jun; 53(6): 637–42PubMedCrossRefGoogle Scholar
  36. 36.
    Bailey DG, Arnold JM, Strong HA, et al. Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics. Clin Pharmacol Ther 1993 Dec; 54(6): 589–94PubMedCrossRefGoogle Scholar
  37. 37.
    Bailey DG, Dresser GK, Kreeft JH, et al. Grapefruitfelodipine interaction: effect of unprocessed fruit and probable active ingredients. Clin Pharmacol Ther 2000 Nov; 68(5): 468–77PubMedCrossRefGoogle Scholar
  38. 38.
    Paine MF, Criss AB, Watkins PB. Two major grapefruit juice components differ in intestinal CYP3A4 inhibition kinetic and binding properties. Drug Metab Dispos 2004 Oct; 32(10): 1146–53PubMedCrossRefGoogle Scholar
  39. 39.
    Paine MF, Criss AB, Watkins PB. Two major grapefruit juice components differ in time to onset of intestinal CYP3A4 inhibition. J Pharmacol Exp Ther 2005 Mar; 312(3): 1151–60PubMedCrossRefGoogle Scholar
  40. 40.
    Paine MF, Widmer WW, Hart HL, et al. A furanocoumarinfree grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interaction. Am J Clin Nutr 2006 May; 83(5): 1097–105PubMedGoogle Scholar
  41. 41.
    Girennavar B, Jayaprakasha GK, Patil BS. Potent inhibition of human cytochrome P450 3A4, 2D6, and 2C9 isoenzymes by grapefruit juice and its furocoumarins. J Food Sci 2007 Oct; 72(8): C417–21PubMedCrossRefGoogle Scholar
  42. 42.
    Tassaneeyakul W, Guo LQ, Fukuda K, et al. Inhibition selectivity of grapefruit juice components on human cytochromes P450. Arch Biochem Biophys 2000 Jun 15; 378(2): 356–63PubMedCrossRefGoogle Scholar
  43. 43.
    Fuhr U, Klittich K, Staib AH. Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br J Clin Pharmacol 1993 Apr; 35(4): 431–6PubMedCrossRefGoogle Scholar
  44. 44.
    Lin HL, Kent UM, Hollenberg PF. The grapefruit juice effect is not limited to cytochrome P450 (P450) 3A4: evidence for bergamottin-dependent inactivation, heme destruction, and covalent binding to protein in P450s 2B6 and 3A5. J Pharmacol Exp Ther 2005 Apr; 313(1): 154–64PubMedCrossRefGoogle Scholar
  45. 45.
    Baumgart A, Schmidt M, Schmitz HJ, et al. Natural furocoumarins as inducers and inhibitors of cytochrome P450 1A1 in rat hepatocytes. Biochem Pharmacol 2005 Feb 15; 69(4): 657–67PubMedCrossRefGoogle Scholar
  46. 46.
    Tassaneeyakul W, Vannaprasaht S, Yamazoe Y. Formation of omeprazole sulphone but not 5-hydroxyomeprazole is inhibited by grapefruit juice. Br J Clin Pharmacol 2000 Feb; 49(2): 139–44PubMedCrossRefGoogle Scholar
  47. 47.
    Uno T, Yasui-Furukori N, Takahata T, et al. Lack of significant effect of grapefruit juice on the pharmacokinetics of lansoprazole and its metabolites in subjects with different CYP2C19 genotypes. J Clin Pharmacol 2005 Jun; 45(6): 690–4PubMedCrossRefGoogle Scholar
  48. 48.
    Lane HY, Jann MW, Chang YC, et al. Repeated ingestion of grapefruit juice does not alter clozapine’s steady-state plasma levels, effectiveness, and tolerability. J Clin Psychiatry 2001 Oct; 62(10): 812–7PubMedCrossRefGoogle Scholar
  49. 49.
    Fuhr U, Maier A, Keller A, et al. Lacking effect of grapefruit juice on theophylline pharmacokinetics. Int J Clin Pharmacol Ther 1995 Jun; 33(6): 311–4PubMedGoogle Scholar
  50. 50.
    Oesterheld J, Kallepalli BR. Grapefruit juice and clomipramine: shifting metabolitic ratios. J Clin Psychopharmacol 1997 Feb; 17(1): 62–3PubMedCrossRefGoogle Scholar
  51. 51.
    Sullivan DM, Ford MA, Boyden TW. Grapefruit juice and the response to warfarin. Am J Health Syst Pharm 1998 Aug 1; 55(15): 1581–3PubMedGoogle Scholar
  52. 52.
    Takanaga H, Ohnishi A, Matsuo H, et al. Inhibition of vinblastine efflux mediated by P-glycoprotein by grapefruit juice components in caco-2 cells. Biol Pharm Bull 1998 Oct; 21(10): 1062–6PubMedCrossRefGoogle Scholar
  53. 53.
    Ikegawa T, Ushigome F, Koyabu N, et al. Inhibition of P-glycoprotein by orange juice components, polymethoxyflavones in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells. Cancer Lett 2000 Nov 10; 160(1): 21–8PubMedCrossRefGoogle Scholar
  54. 54.
    Edwards DJ, Bernier SM. Naringin and naringenin are not the primary CYP3A inhibitors in grapefruit juice. Life Sci 1996; 59(13): 1025–30PubMedCrossRefGoogle Scholar
  55. 55.
    Takanaga H, Ohnishi A, Yamada S, et al. Polymethoxylated flavones in orange juice are inhibitors of P-glycoprotein but not cytochrome P450 3A4. J Pharmacol Exp Ther 2000 Apr; 293(1): 230–6PubMedGoogle Scholar
  56. 56.
    Honda Y, Ushigome F, Koyabu N, et al. Effects of grapefruit juice and orange juice components on P-glycoprotein- and MRP2-mediated drug efflux. Br J Pharmacol 2004 Dec; 143(7): 856–64PubMedCrossRefGoogle Scholar
  57. 57.
    de Castro WV, Mertens-Talcott S, Derendorf H, et al. Grapefruit juice-drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells. J Pharm Sci 2007 Oct; 96(10): 2808–17PubMedCrossRefGoogle Scholar
  58. 58.
    Dahan A, Amidon GL. Grapefruit juice and its constituents augment colchicine intestinal absorption: potential hazardous interaction and the role of p-glycoprotein. Pharm Res 2009 Apr; 26(4): 883–92PubMedCrossRefGoogle Scholar
  59. 59.
    Becquemont L, Verstuyft C, Kerb R, et al. Effect of grapefruit juice on digoxin pharmacokinetics in humans. Clin Pharmacol Ther 2001 Oct; 70(4): 311–6PubMedGoogle Scholar
  60. 60.
    Dresser GK, Bailey DG, Leake BF, et al. Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine. Clin Pharmacol Ther 2002 Jan; 71(1): 11–20PubMedCrossRefGoogle Scholar
  61. 61.
    Glaeser H, Bailey DG, Dresser GK, et al. Intestinal drug transporter expression and the impact of grapefruit juice in humans. Clin Pharmacol Ther 2007 Mar; 81(3): 362–70PubMedCrossRefGoogle Scholar
  62. 62.
    Satoh H, Yamashita F, Tsujimoto M, et al. Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos 2005 Apr; 33(4): 518–23PubMedCrossRefGoogle Scholar
  63. 63.
    Lilja JJ, Niemi M, Fredrikson H, et al. Effects of clarithromycin and grapefruit juice on the pharmacokinetics of glibenclamide. Br J Clin Pharmacol 2007 Jun; 63(6): 732–40PubMedCrossRefGoogle Scholar
  64. 64.
    Lilja JJ, Backman JT, Laitila J, et al. Itraconazole increases but grapefruit juice greatly decreases plasma concentrations of celiprolol. Clin Pharmacol Ther 2003 Mar; 73(3): 192–8PubMedCrossRefGoogle Scholar
  65. 65.
    Schwarz UI, Seemann D, Oertel R, et al. Grapefruit juice ingestion significantly reduces talinolol bioavailability. Clin Pharmacol Ther 2005 Apr; 77(4): 291–301PubMedCrossRefGoogle Scholar
  66. 66.
    Kato Y, Miyazaki T, Kano T, et al. Involvement of influx and efflux transport systems in gastrointestinal absorption of celiprolol. J Pharm Sci 2009 Jul; 98(7): 2529–39PubMedCrossRefGoogle Scholar
  67. 67.
    Shirasaka Y, Kuraoka E, Spahn-Langguth H, et al. Species difference in the effect of grapefruit juice on intestinal absorption of talinolol between human and rat. J Pharmacol Exp Ther 2010 Jan; 332(1): 181–9PubMedCrossRefGoogle Scholar
  68. 68.
    Tapaninen T, Neuvonen PJ, Niemi M. Grapefruit juice greatly reduces the plasma concentrations of the OATP2B1 and CYP3A4 substrate aliskiren. Clin Pharmacol Ther 2010 Sep; 88(3): 339–42PubMedCrossRefGoogle Scholar
  69. 69.
    Bailey DG, Dresser GK, Leake BF, et al. Naringin is a major and selective clinical inhibitor of organic aniontransporting polypeptide 1A2 (OATP1A2) in grapefruit juice. Clin Pharmacol Ther 2007 Apr; 81(4): 495–502PubMedCrossRefGoogle Scholar
  70. 70.
    Nishimuta H, Ohtani H, Tsujimoto M, et al. Inhibitory effects of various beverages on human recombinant sulfotransferase isoforms SULT1A1 and SULT1A3. Biopharm Drug Dispos 2007 Dec; 28(9): 491–500PubMedCrossRefGoogle Scholar
  71. 71.
    Li P, Callery PS, Gan LS, et al. Esterase inhibition attribute of grapefruit juice leading to a new drug interaction. Drug Metab Dispos 2007 Jul; 35(7): 1023–31PubMedCrossRefGoogle Scholar
  72. 72.
    Dresser GK, Kim RB, Bailey DG. Effect of grapefruit juice volume on the reduction of fexofenadine bioavailability: possible role of organic anion transporting polypeptides. Clin Pharmacol Ther 2005 Mar; 77(3): 170–7PubMedCrossRefGoogle Scholar
  73. 73.
    De Castro WV, Mertens-Talcott S, Rubner A, et al. Variation of flavonoids and furanocoumarins in grapefruit juices: a potential source of variability in grapefruit juicedrug interaction studies. J Agric Food Chem 2006 Jan 11; 54(1): 249–55PubMedCrossRefGoogle Scholar
  74. 74.
    Garg SK, Kumar N, Bhargava VK, et al. Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy. Clin Pharmacol Ther 1998 Sep; 64(3): 286–8PubMedCrossRefGoogle Scholar
  75. 75.
    Tegretol Retard (carbamazepine 200mg, 400mg tablets): summary of product characterisitics. Novartis Pharmaceuticals UK Ltd. Updated 09/12/2009 [online]. Available from URL: http://www.medicines.org.uk 1330 [Accessed 2010 Feb 1]
  76. 76.
    Tegretol® (carbamazepine) tablets, suspension: US prescribing information. Novartis Pharmaceutical corp. Revised February 2009 [online]. Available from URL: http://www.pharma.us.novartis.com/product/pi/pdf/tegretol.pdf [Accessed 2010 Jul 17]
  77. 77.
    Banfield C, Gupta S, Marino M, et al. Grapefruit juice reduces the oral bioavailability of fexofenadine but not desloratadine. Clin Pharmacokinet 2002; 41(4): 311–8PubMedCrossRefGoogle Scholar
  78. 78.
    Telfast (fexofenadine) tablets: summary of product characteristics, sanofi-aventis. Updated 06/01/2009 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jan 3]
  79. 79.
    Allegra (fexofenadine) tablets: US prescribing information. sanofi-aventis US. Updated 07/2007 [online]. Available from URL: http://products.sanofi-aventis.us/allegra/allegra_ODT.pdf [Accessed 2010 Jul 15]
  80. 80.
    van Agtmael MA, Gupta V, van der Graaf CA, et al. The effect of grapefruit juice on the time-dependent decline of artemether plasma levels in healthy subjects. Clin Pharmacol Ther 1999 Oct; 66(4): 408–14PubMedCrossRefGoogle Scholar
  81. 81.
    van Agtmael MA, Gupta V, van der Wosten TH, et al. Grapefruit juice increases the bioavailability of artemether. Eur J Clin Pharmacol 1999 Jul; 55(5): 405–10PubMedCrossRefGoogle Scholar
  82. 82.
    Riamet (artemether/lumefantrine 20/120mg tablets): summary of product characteristics. Novartis Pharmaceuticals UK Ltd. Updated 21/09/2009 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Feb 1]
  83. 83.
    Coartem (artemether/lumefantrine) tablets: US prescribing information. Novartis Pharmaceuticals Corp. Updated February 2010 [online]. Available from URL: http://www.pharma.us.novartis.com/product/pi/pdf/coartem.pdf [Accessed 2010 Jul 16]
  84. 84.
    Cuong BT, Binh VQ, Dai B, et al. Does gender, food or grapefruit juice alter the pharmacokinetics of primaquine in healthy subjects? Br J Clin Pharmacol 2006 Jun; 61(6): 682–9PubMedCrossRefGoogle Scholar
  85. 85.
    Primaquine phosphate tablets, USP: US prescribing information. Sanofi-Synthelabo Inc. Revised April 2003 [online]. Available from URL: http://products.sanofiaventis.us/primaquine/primaquine.html [Accessed 2010 Jul 17]
  86. 86.
    Orap (pimozide) 4mg tablets: summary of product characteristics. Janssen-Cilag Ltd. Updated 15/02/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Sep 28]
  87. 87.
    Andersen V, Pedersen N, Larsen NE, et al. Intestinal first pass metabolism of midazolam in liver cirrhosis: effect of grapefruit juice. Br J Clin Pharmacol 2002 Aug; 54(2): 120–4PubMedCrossRefGoogle Scholar
  88. 88.
    Vanakoski J, Mattila MJ, Seppala T. Grapefruit juice does not enhance the effects of midazolam and triazolam in man. Eur J Clin Pharmacol 1996; 50(6): 501–8PubMedCrossRefGoogle Scholar
  89. 89.
    Sugimoto K, Araki N, Ohmori M, et al. Interaction between grapefruit juice and hypnotic drugs: comparison of triazolam and quazepam. Eur J Clin Pharmacol 2006 Mar; 62(3): 209–15PubMedCrossRefGoogle Scholar
  90. 90.
    Halcion® (triazolam) tablets: US prescribing information. Pfizer Inc. Updated 12/2008 [online]. Available from URL: http://media.pfizer.com/files/products/uspi_halcion.pdf [Accessed 2010 Jul 26]
  91. 91.
    Gammans RE, Mayol RF, Mackenthun AV, et al. The relationship between buspirone bioavailability and dose in healthy subjects. Biopharm Drug Dispos 1985 Apr–Jun; 6(2): 139–45PubMedCrossRefGoogle Scholar
  92. 92.
    Lilja JJ, Kivisto KT, Backman JT, et al. Grapefruit juice substantially increases plasma concentrations of buspirone. Clin Pharmacol Ther 1998 Dec; 64(6): 655–60PubMedCrossRefGoogle Scholar
  93. 93.
    Buspar (buspirone 5mg and 10mg tablets): patient information leaflet. E. R. Squibb & Sons Limited. Updated 10/03/2009 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Feb 1]
  94. 94.
    BuSpar® (buspirone hydrochloride tablets USP) tablets: US prescribing information. Bristol-Myers Squibb Company. Revised March 2007 [online]. Available from URL: http://packageinserts.bms.com/pi/pi_buspar.pdf [Accessed 2010 Jul 15]
  95. 95.
    Libersa CC, Brique SA, Motte KB, et al. Dramatic inhibition of amiodarone metabolism induced by grapefruit juice. Br J Clin Pharmacol 2000 Apr; 49(4): 373–8PubMedCrossRefGoogle Scholar
  96. 96.
    Codarone (amiodarone) tablets: summary of product characteristics. sanofi-aventis. Updated 15/07/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 26]
  97. 97.
    Cordarone® (amiodarone HCl) tablets: US prescribing information. Wyeth Pharmaceuticals Inc. Updated 08/2009 [online]. Available from URL: http://www.wyeth.com/content/showlabeling.asp?id=93 [Accessed 2010 Jul 26]
  98. 98.
    Arythmol (propafenone 150mg and 300mg tablets): summary of product characteristics. Abbott Laboratories Ltd. Updated 08/01/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Feb 1]
  99. 99.
    Rhythmol® (propafenone hydrochloride) tablets: US prescribing information. GlaxoSmithKline. October 2009 [online]. Available from URL: http://us.gsk.com/products/assets/us_rythmol.pdf [Accessed 2010 Jul 17]
  100. 100.
    Multaq (dronedarone) 400mg tablets: summary of product characteristics. Sanofi-Aventis. Updated 31/03/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Sep 28]
  101. 101.
    Multaq (dronedarone) 400mg tablets: US prescribing information, sanofi-aventis. Issued July 2009 [online]. Available from URL: http://products.sanofi-aventis.us/Multaq/Multaq.pdf [Accessed 2010 Sep 28]
  102. 102.
    Fuhr U, Muller-Peltzer H, Kern R, et al. Effects of grapefruit juice and smoking on verapamil concentrations in steady state. Eur J Clin Pharmacol 2002 Apr; 58(1): 45–53PubMedCrossRefGoogle Scholar
  103. 103.
    Ho PC, Ghose K, Saville D, et al. Effect of grapefruit juice on pharmacokinetics and pharmacodynamics of verapamil enantiomers in healthy volunteers. Eur J Clin Pharmacol 2000 Dec; 56(9–10): 693–8PubMedCrossRefGoogle Scholar
  104. 104.
    Zaidenstein R, Dishi V, Gips M, et al. The effect of grapefruit juice on the pharmacokinetics of orally administered verapamil. Eur J Clin Pharmacol 1998 Jun; 54(4): 337–40PubMedCrossRefGoogle Scholar
  105. 105.
    Covera-HS (verapamil hydrochloride) controlled release tablets: US prescribing information. Pfizer Inc. Revised February 2010 [online]. Available from URL: http://www.pfizer.com/files/products/uspi_covera.pdf [Accessed 2010 Jul 15]
  106. 106.
    Nakagawa K, Goto T. Effects of ingestion of grapefruit juice or grapefruit on the hypotensive effect and plasma concentrations of dihydropyridine calcium antagonists (amlodipine and nifedipine): a case study. Clin Exp Hypertens 2010 Jan; 32(2): 71–5PubMedCrossRefGoogle Scholar
  107. 107.
    Josefsson M, Zackrisson AL, Ahlner J. Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers. Eur J Clin Pharmacol 1996; 51(2): 189–93PubMedCrossRefGoogle Scholar
  108. 108.
    Vincent J, Harris SI, Foulds G, et al. Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine. Br J Clin Pharmacol 2000 Nov; 50(5): 455–63PubMedCrossRefGoogle Scholar
  109. 109.
    Amlostin (amlodipine maleate) tablets: summary of product characteristics. Discovery Pharmaceuticals Ltd. Updated 19/02/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 22]
  110. 110.
    Norvasc (amlodipine besylate) tablets: US prescribing information. Pfizer Inc. Revised March 2010 [online]. Available from URL: http://www.pfizer.com/files/products/uspi_norvasc.pdf [Accessed 2010 Jul 22]
  111. 111.
    Istin (amlodipine besilate) tablets: summary of product characteristics. Pfizer Ltd. Updated 01/04/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 22]
  112. 112.
    Bailey DG, Arnold JM, Bend JR, et al. Grapefruit juicefelodipine interaction: reproducibility and characterization with the extended release drug formulation. Br J Clin Pharmacol 1995 Aug; 40(2): 135–40PubMedGoogle Scholar
  113. 113.
    Bailey DG, Kreeft JH, Munoz C, et al. Grapefruit juicefelodipine interaction: effect of naringin and 6′,7′-dihydroxybergamottin in humans. Clin Pharmacol Ther 1998 Sep; 64(3): 248–56PubMedCrossRefGoogle Scholar
  114. 114.
    Malhotra S, Bailey DG, Paine MF, et al. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther 2001 Jan; 69(1): 14–23PubMedCrossRefGoogle Scholar
  115. 115.
    Dresser GK, Bailey DG, Carruthers SG. Grapefruit juice: felodipine interaction in the elderly. Clin Pharmacol Ther 2000 Jul; 68(1): 28–34PubMedCrossRefGoogle Scholar
  116. 116.
    Edgar B, Bailey D, Bergstrand R, et al. Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine: and its potential clinical relevance. Eur J Clin Pharmacol 1992; 42(3): 313–7PubMedCrossRefGoogle Scholar
  117. 117.
    Uno T, Ohkubo T, Sugawara K, et al. Effects of grapefruit juice on the stereoselective disposition of nicardipine in humans: evidence for dominant presystemic elimination at the gut site. Eur J Clin Pharmacol 2000 Dec; 56(9–10): 643–9PubMedCrossRefGoogle Scholar
  118. 118.
    Cardene SR (nicardipine hydrochloride) sustained release capsules: summary of product characteristics. Astellas Pharma Ltd. Updated 19/04/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 22]
  119. 119.
    Fuhr U, Maier-Bruggemann A, Blume H, et al. Grapefruit juice increases oral nimodipine bioavailability. Int J Clin Pharmacol Ther 1998 Mar; 36(3): 126–32PubMedGoogle Scholar
  120. 120.
    Nimotop (nimodipine) tablets: summary of product characteristics. Bayer Plc. Updated 17/06/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 22]
  121. 121.
    Odou P, Ferrari N, Barthelemy C, et al. Grapefruit juicenifedipine interaction: possible involvement of several mechanisms. J Clin Pharm Ther 2005 Apr; 30(2): 153–8PubMedCrossRefGoogle Scholar
  122. 122.
    Rashid J, McKinstry C, Renwick AG, et al. Quercetin, an in vitro inhibitor of CYP3A, does not contribute to the interaction between nifedipine and grapefruit juice. Br J Clin Pharmacol 1993 Nov; 36(5): 460–3PubMedCrossRefGoogle Scholar
  123. 123.
    Adigun AQ, Mudasiru Z. Clinical effects of grapefruit juice-nifedipine interaction in a 54-year-old Nigerian: a case report. J Natl Med Assoc 2002 Apr; 94(4): 276–8PubMedGoogle Scholar
  124. 124.
    Adalat (nifedipine) capsules: summary of product characteristics. Bayer Plc. Updated 01/07/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 22]
  125. 125.
    Procardia® (nifedipine) capsules: US prescribing information. Pfizer Inc. Revised March 2006 [online]. Available from URL: http://www.pfizer.com/files/products/uspi_procardia.pdf [Accessed 2010 Jul 22]
  126. 126.
    Prescal (isradipine) tablets: summary of product characteristics. Novartis Pharmaceuticals UK Ltd. Updated 12/12/2007 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 26]
  127. 127.
    Motens (lacidipine) tablets: summary of product characteristics. Boehringer Ingelheim Ltd. Updated 24/05/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 26]
  128. 128.
    Lercanidipine tablets: summary of product characteristics. Winthrop Pharmaceuticals UK Ltd. Updated 03/02/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 26]
  129. 129.
    DYNACIRC CR (isradipine) controlled release tablets: US prescribing information. GlaxoSmithKline. February 2009 [online]. Available from URL: http://us.gsk.com/products/assets/us_dynacirc_cr.pdf [Accessed 2010 Jul 15]
  130. 130.
    Takanaga H, Ohnishi A, Murakami H, et al. Relationship between time after intake of grapefruit juice and the effect on pharmacokinetics and pharmacodynamics of nisoldipine in healthy subjects. Clin Pharmacol Ther 2000 Mar; 67(3): 201–14PubMedCrossRefGoogle Scholar
  131. 131.
    Sular (nisoldipine) extended release tablet: US prescribing information. Shionogi Pharma, Inc. Revised 02/2010 [online]. Available from URL: http://www.sular.com/pdf/Sular_PI.pdf [Accessed 2010 Jul 17]
  132. 132.
    Fukazawa I, Uchida N, Uchida E, et al. Effects of grapefruit juice on pharmacokinetics of atorvastatin and pravastatin in Japanese. Br J Clin Pharmacol 2004 Apr; 57(4): 448–55PubMedCrossRefGoogle Scholar
  133. 133.
    Ando H, Tsuruoka S, Yanagihara H, et al. Effects of grapefruit juice on the pharmacokinetics of pitavastatin and atorvastatin. Br J Clin Pharmacol 2005 Nov; 60(5): 494–7PubMedCrossRefGoogle Scholar
  134. 134.
    Lipitor (atorvastatin calcium) tablets: US prescribing information. Pfizer Inc. Updated 06/2009 [online]. Available from URL: http://www.pfizer.com/files/products/uspi_lipitor.pdf [Accessed 2010 Jul 13]
  135. 135.
    Kantola T, Kivisto KT, Neuvonen PJ. Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther 1998 Apr; 63(4): 397–402PubMedCrossRefGoogle Scholar
  136. 136.
    Mevacor (lovastatin) tablets: US prescribing information. Merck & Co Inc. Issued May 2010 [online]. Available from URL: http://www.merck.com/product/usa/pi_circulars/m/mevacor/mevacor_pi.pdf [Accessed 2010 Jul 15]
  137. 137.
    Lilja JJ, Neuvonen M, Neuvonen PJ. Effects of regular iconsumption of grapefruit juice on the pharmacokinetics of simvastatin. Br J Clin Pharmacol 2004 Jul; 58(1): 56–60PubMedCrossRefGoogle Scholar
  138. 138.
    Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juicesimvastatin interaction: effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Clin Pharmacol Ther 1998 Nov; 64(5): 477–83PubMedCrossRefGoogle Scholar
  139. 139.
    Lilja JJ, Kivisto KT, Neuvonen PJ. Duration of effect of grapefruit juice on the pharmacokinetics of the CYP3A4 substrate simvastatin. Clin Pharmacol Ther 2000 Oct; 68(4): 384–90PubMedCrossRefGoogle Scholar
  140. 140.
    Dreier JP, Endres M. Statin-associated rhabdomyolysis triggered by grapefruit consumption. Neurology 2004 Feb 24; 62(4): 670PubMedCrossRefGoogle Scholar
  141. 141.
    Zocor Heart-Pro (simvastatin 10mg film coated tablets). McNeil Ltd. Updated 06/11/2009 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Feb 1]
  142. 142.
    Zocor (simvastatin) tablets: US prescribing information. Merck & Co Inc. Issued May 2010 [online]. Available from URL: http://www.merck.com/product/usa/pi_circulars/z/zocor/zocor_pi.pdf [Accessed 2010 Jul 13]
  143. 143.
    Procoralan (ivabradine 5mg and 7.5mg film coated tablets): summary of product characteristics. Servier Laboratories Limited. Updated 13/11/2009 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Feb 1]
  144. 144.
    Ranexa (ranolazine 375mg, 500mg and 750mg prolongedrelease tablets): summary of product characteristics. A.Menarini Pharma U.K. S.R.L. Updated 10/08/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Feb 1]
  145. 145.
    Ranexa (ranolazine) extended release tablets: US prescribing information. Gilead Sciences Inc. Revised 09/2009 [online]. Available from URL: http://www.ranexa.com/download/RanexaPI.PDF [Accessed 2010 Jul 22]
  146. 146.
    EntocortCR (budesonide) 3mg capsules: summary of product characteristics. AstraZeneca UK Limited. Updated 26/11/2009 [online]. Available from URL: http://www.medicines.org.uk [Accessed 28/09/2010]
  147. 147.
    EntocortEC (budesonide) 3mg capsules. AstraZeneca. Revised 06/2009 [online]. Available from URL: http://www1.astrazeneca-us.com/pi/entocortec.pdf [Accessed 2010 Sep 28]
  148. 148.
    Yin OQ, Gallagher N, Li A, et al. Effect of grapefruit juice on the pharmacokinetics of nilotinib in healthy participants. J Clin Pharmacol 2010 Feb; 50(2): 188–94PubMedCrossRefGoogle Scholar
  149. 149.
    Tasigna (nilotinib) capsules: summary of product characteristics. Novartis Pharmaceuticals UK Ltd. Updated 03/03/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 22]
  150. 150.
    Tasigna (nilotinib) capsules: US prescribing information. Novartis Inc. Updated 06/2010 [online]. Available from URL: http://www.pharma.us.novartis.com/product/pi/pdf/tasigna.pdf [Accessed 2010 Jul 22]
  151. 151.
    Tyverb (lapatinib) tablets: summary of product characteristics. GlaxoSmithKline UK. Updated 24/06/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 22]
  152. 152.
    Tykerb (lapatinib) tablets: summary of product characteristics. GlaxoSmithKline. Revised April 2010 [online]. Available from URL: http://us.gsk.com/products/assets/us_tykerb.pdf [Accessed 2010 Jul 22]
  153. 153.
    Sutent (sunitinib) capsules: summary of product characteristics. Pfizer Ltd. Updated 09/07/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 22]
  154. 154.
    Sutent (sunitinib maleate) capsules: US prescribing information. Pfizer Inc. Issued July 2010 [online]. Available from URL: http://www.pfizer.com/files/products/uspi_sutent.pdf [Accessed 2010 Jul 22]
  155. 155.
    Sprycel (dasatinib) tablets: US prescribing information. Bristol-Myers Squibb Company. Updated 06/2009 [online]. Available from URL: http://packageinserts.bms.com/pi/pi_sprycel.pdf [Accessed 2010 Jul 22]
  156. 156.
    Tarceva (erlotinib) tablets: US prescribing information. OSI Pharmaceuticals Inc. Revised 04/2010 [online]. Available from URL: http://www.osip.com/pdf/Tarceva_PI_042010.pdf [Accessed 2010 Jul 22]
  157. 157.
    Gleevec (imatinib mesylate) tablets: US prescribing information. Novartis Inc. Updated 02/2010 [online]. Available from URL: http://www.pharma.us.novartis.com/product/pi/pdf/gleevec_tabs.pdf [Accessed 2010 Jul 22]
  158. 158.
    Torisel (temsirolimus) IV injection: US prescribing information. Wyeth Pharmaceuticals Inc. Revised 07/2010 [online]. Available from URL: http://www.wyeth.com/content/showlabeling.asp?id=490 [Accessed 2010 Jul 22]
  159. 159.
    Kivisto KT, Lilja JJ, Backman JT, et al. Repeated consumption of grapefruit juice considerably increases plasma concentrations of cisapride. Clin Pharmacol Ther 1999 Nov; 66(5): 448–53PubMedCrossRefGoogle Scholar
  160. 160.
    Propulsid (cisapride) official FDA information. FDA Professional Drug information. Updated 10/2009 [online]. Available from URL: http://www.drugs.com/pro/propulsid.html [Accessed 2010 Jul 13]
  161. 161.
    Bistrup C, Nielsen FT, Jeppesen UE, et al. Effect of grapefruit juice on Sandimmun Neoral absorption among stable renal allograft recipients. Nephrol Dial Transplant 2001 Feb; 16(2): 373–7PubMedCrossRefGoogle Scholar
  162. 162.
    Brunner LJ, Pai KS, Munar MY, et al. Effect of grapefruit juice on cyclosporin A pharmacokinetics in pediatric renal transplant patients. Pediatr Transplant 2000 Nov; 4(4): 313–21PubMedCrossRefGoogle Scholar
  163. 163.
    Ducharme MP, Provenzano R, Dehoorne-Smith M, et al. Trough concentrations of cyclosporine in blood following administration with grapefruit juice. Br J Clin Pharmacol 1993 Nov; 36(5): 457–9PubMedCrossRefGoogle Scholar
  164. 164.
    Edwards DJ, Fitzsimmons ME, Schuetz EG, et al. 6′,7′-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Clin Pharmacol Ther 1999 Mar; 65(3): 237–44PubMedCrossRefGoogle Scholar
  165. 165.
    Ku YM, Min DI, Flanigan M. Effect of grapefruit juice on the pharmacokinetics of microemulsion cyclosporine and its metabolite in healthy volunteers: does the formulation difference matter? J Clin Pharmacol 1998 Oct; 38(10): 959–65PubMedGoogle Scholar
  166. 166.
    Lee M, Min DI, Ku YM, et al. Effect of grapefruit juice on pharmacokinetics of microemulsion cyclosporine in African American subjects compared with Caucasian subjects: does ethnic difference matter? J Clin Pharmacol 2001 Mar; 41(3): 317–23PubMedCrossRefGoogle Scholar
  167. 167.
    Mehrsai AR, Pourmand G, Mansour D, et al. Effect of grapefruit juice on serum concentration of cyclosporine in Iranian renal transplant patients. Transplant Proc 2003 Nov; 35(7): 2739–41PubMedCrossRefGoogle Scholar
  168. 168.
    Proppe DG, Hoch OD, McLean AJ, et al. Influence of chronic ingestion of grapefruit juice on steady-state blood concentrations of cyclosporine A in renal transplant patients with stable graft function. Br J Clin Pharmacol 1995 Mar; 39(3): 337–8PubMedCrossRefGoogle Scholar
  169. 169.
    Paine MF, Widmer WW, Pusek SN, et al. Further characterization of a furanocoumarin-free grapefruit juice on drug disposition: studies with cyclosporine. Am J Clin Nutr 2008 Apr 1; 87(4): 863–71PubMedGoogle Scholar
  170. 170.
    Schwarz UI, Johnston PE, Bailey DG, et al. Impact of citrus soft drinks relative to grapefruit juice on ciclosporin disposition. Br J Clin Pharmacol 2006 Oct; 62(4): 485–91PubMedCrossRefGoogle Scholar
  171. 171.
    Neoral (ciclosporin) capsules/oral solution: US prescribing information. Novartis Pharmaceuticals Corp. Revised October 2009 [online]. Available from URL: http://www.pharma.us.novartis.com/product/pi/pdf/neoral.pdf [Accessed 2010 Jul 17]
  172. 172.
    Liu C, Shang YF, Zhang XF, et al. Co-administration of grapefruit juice increases bioavailability of tacrolimus in liver transplant patients: a prospective study. Eur J Clin Pharmacol 2009 Sep; 65(9): 881–5PubMedCrossRefGoogle Scholar
  173. 173.
    Fukatsu S, Fukudo M, Masuda S, et al. Delayed effect of grapefruit juice on pharmacokinetics and pharmacodynamics of tacrolimus in a living-donor liver transplant recipient. Drug Metab Pharmacokinet 2006 Apr; 21(2): 122–5PubMedCrossRefGoogle Scholar
  174. 174.
    Peynaud D, Charpiat B, Vial T, et al. Tacrolimus severe overdosage after intake of masked grapefruit in orange marmalade. Eur J Clin Pharmacol 2007 Jul; 63(7): 721–2PubMedCrossRefGoogle Scholar
  175. 175.
    Prograf (tacrolimus) capsules: summary of product characteristics. Astellas Pharma Ltd. Updated 25/05/2009 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Feb 2]
  176. 176.
    Prograf® (tacrolimus) capsules: US prescribing information. Astellas Pharma US Inc. Revised August 2009 [online]. Available from URL: http://www.astellas.us/docs/prograf.pdf [Accessed 2010 Jul 17]
  177. 177.
    Rapamune (sirolimus) tablets: summary of product characteristics. Wyeth Pharmaceuticals. Updated 27/07/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 27]
  178. 178.
    Rapamune (sirolimus) tablets: US prescribing information. Wyeth Pharmaceuticals Inc. Updated 07/2010 [online]. Available from URL: http://www.wyeth.com/content/showlabeling.asp?id=139 [Accessed 2010 Jul 27]
  179. 179.
    Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. Effects of grapefruit juice on the pharmacokinetics of sildenafil. Clin Pharmacol Ther 2002 Jan; 71(1): 21–9PubMedCrossRefGoogle Scholar
  180. 180.
    Lee M, Min DI. Determination of sildenafil citrate in plasma by high-performance liquid chromatography and a case for the potential interaction of grapefruit juice with sildenafil citrate. Ther Drug Monit 2001 Feb; 23(1): 21–6PubMedCrossRefGoogle Scholar
  181. 181.
    Viagra (sildenafil citrate) tablets: summary of product characteristics. Pfizer Ltd. Updated 19/07/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 27]
  182. 182.
    Viagra® (sildenafil citrate) tablets: US prescribing information. Pfizer Inc. January 2010 [online]. Available from URL: http://www.pfizer.com/files/products/uspi_viagra.pdf [Accessed 2010 Jul 16]
  183. 183.
    Cialis (tadalafil) tablets: summary of product characteristics. Eli Lilly and Company Limited. Updated 23/04/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 27]
  184. 184.
    Cialis (tadalafil) tablet: US prescribing information. Eli Lilly &Co. Revised February 1, 2010 [online]. Available from URL: http://pi.lilly.com/us/cialis-pi.pdf [Accessed 2010 Jul 13]
  185. 185.
    Levitra (vardenafil) tablets: summary of product characteristics. Bayer Plc. Updated 16/07/2009 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jan 13]
  186. 186.
    Levitra (vardenafil) tablets: US prescribing information. Bayer Healthcare Pharmaceuticals Inc. Updated 05/2010 [online]. Available from URL: http://www.univgraph.com/bayer/inserts/levitra.pdf [Accessed 2010 Jul 17]
  187. 187.
    Emselex (darifenacin) prolonged release tablets: summary of product characteristics. Novartis Pharmaceuticals UK Ltd. Updated 25/03/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Sep 28]
  188. 188.
    Castro N, Jung H, Medina R, et al. Interaction between grapefruit juice and praziquantel in humans. Antimicrob Agents Chemother 2002 May; 46(5): 1614–6PubMedCrossRefGoogle Scholar
  189. 189.
    Nagy J, Schipper HG, Koopmans RP, et al. Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability. Am J Trop Med Hyg 2002 Mar; 66(3): 260–3PubMedGoogle Scholar
  190. 190.
    Awadzi K, Hero M, Opoku NO, et al. The chemotherapy of onchocerciasis XVII. A clinical evaluation of albendazole in patients with onchocerciasis; effects of food and pretreatment with ivermectin on drug response and pharmacokinetics. Trop Med Parasitol 1994 Sep; 45(3): 203–8Google Scholar
  191. 191.
    Cheng KL, Nafziger AN, Peloquin CA, et al. Effect of grapefruit juice on clarithromycin pharmacokinetics. Antimicrob Agents Chemother 1998 Apr; 42(4): 927–9PubMedGoogle Scholar
  192. 192.
    Kanazawa S, Ohkubo T, Sugawara K. The effects of grapefruit juice on the pharmacokinetics of erythromycin. Eur J Clin Pharmacol 2001 Jan–Feb; 56(11): 799–803PubMedCrossRefGoogle Scholar
  193. 193.
    Abbas R, Chow CP, Browder NJ, et al. In vitro metabolism and interaction of cilostazol with human hepatic cytochrome P450 isoforms. Hum Exp Toxicol 2000 Mar; 19(3): 178–84PubMedCrossRefGoogle Scholar
  194. 194.
    Taniguchi K, Ohtani H, Ikemoto T, et al. Possible case of potentiation of the antiplatelet effect of cilostazol by grapefruit juice. J Clin Pharm Ther 2007 Oct; 32(5): 457–9PubMedCrossRefGoogle Scholar
  195. 195.
    Pletal (cilostazol) 50mg tablets: summary of product characteristics. Otsuka Pharmaceuticals (UK) Ltd. Updated 03/09/2009 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Feb 1]
  196. 196.
    Pletal (cilostazol) tablets: US prescribing information. Otsuka Pharmaceuticals, Inc. Updated 05/2007 [online]. Available from URL: http://www.otsuka-us.com/documents/Pletal_PI.pdf [Accessed 2010 Jul 19]
  197. 197.
    van Rooij J, van der Meer F, Schoemaker HC, et al. Comparison of the effect of grapefruit juice and cimetidine on pharmacokinetics and anticoagulant effect of a single dose of acenocoumarol [abstract]. Br J Clin Pharmacol 1993; 35: 548PCrossRefGoogle Scholar
  198. 198.
    Brandin H, Myrberg O, Rundlof T, et al. Adverse effects by artificial grapefruit seed extract products in patients on warfarin therapy. Eur J Clin Pharmacol 2007 Jun; 63(6): 565–70PubMedCrossRefGoogle Scholar
  199. 199.
    Nemeroff CB, DeVane CL, Pollock BG. Newer antidepressants and the cytochrome P450 system. Am J Psychiatry 1996 Mar; 153(3): 311–20PubMedGoogle Scholar
  200. 200.
    Stockley’s drug interactions. 9th ed. London: Pharmaceutical Press, 2010 [online]. Available from URL: http://www.medicinescomplete.com [Accessed 2010 Nov 15]
  201. 201.
    Preskorn SH. Clinically relevant pharmacology of selective serotonin reuptake inhibitors: an overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet 1997; 32 Suppl. 1: 1–21PubMedCrossRefGoogle Scholar
  202. 202.
    Obach RS, Cox LM, Tremaine LM. Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study. Drug Metab Dispos 2005 Feb; 33(2): 262–70PubMedCrossRefGoogle Scholar
  203. 203.
    Ueda N, Yoshimura R, Umene-Nakano W, et al. Grapefruit juice alters plasma sertraline levels after single ingestion of sertraline in healthy volunteers. World J Biol Psychiatry 2009; 10 (4 Pt 3): 832–5PubMedCrossRefGoogle Scholar
  204. 204.
    Lee AJ, Chan WK, Harralson AF, et al. The effects of grapefruit juice on sertraline metabolism: an in vitro and in vivo study. Clin Ther 1999 Nov; 21(11): 1890–9PubMedCrossRefGoogle Scholar
  205. 205.
    Fabre LF, Abuzzahab FS, Amin M, et al. Sertraline safety and efficacy in major depression: a double-blind fixeddose comparison with placebo. Biol Psychiatry 1995 Nov 1; 38(9): 592–602PubMedCrossRefGoogle Scholar
  206. 206.
    Sertraline (setraline 50mg and 100mg film coated tablets): summary of product characteristics. Wockhardt UK Ltd. Updated 11/06/2009 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Feb 1]
  207. 207.
    Zoloft (sertraline) tablets/oral solution: US prescribing information. Updated 10/2008 [online]. Available from URL: http://media.pfizer.com/files/products/uspi_zoloft.pdf [Accessed 2010 Jul 16]
  208. 208.
    DeSilva KE, Le Flore DB, Marston BJ, et al. Serotonin syndrome in HIV-infected individuals receiving antiretroviral therapy and fluoxetine. AIDS 2001 Jul 6; 15(10): 1281–5PubMedCrossRefGoogle Scholar
  209. 209.
    Fluoxetine (fluoxetine 20mg capsules): summary of product characteristics. Sandoz Ltd. Updated 23/12/2009 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Feb 1]
  210. 210.
    Prozac (fluoxetine hydrochloride): US prescribing information. Eli Lilly and Company. Revised October 29, 2009 [online]. Available from URL: http://pi.lilly.com/us/prozac.pdf [Accessed 2010 Jan 18]
  211. 211.
    Hori H, Yoshimura R, Ueda N, et al. Grapefruit juicefluvoxamine interaction: is it risky or not? J Clin Psychopharmacol 2003 Aug; 23(4): 422–4PubMedCrossRefGoogle Scholar
  212. 212.
    Fluvoxamine (fluvoxamine 50mg & 100mg film coated tablets): summary of product characteristics. Wockhardt UK Ltd. Updated 02/09/2008 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Feb 1]
  213. 213.
    Luvox® CR (fluvoxamine maleate) extended release capsules: US prescribing information. Solvay Pharmaceuticals Inc. Revised 02/2009 [online]. Available from URL: http://www.luvoxcr.com/LUVOX-CR-PI.pdf [Accessed 2010 Jul 15]
  214. 214.
    Bidstrup TB, Damkier P, Olsen AK, et al. The impact of CYP2C8 polymorphism and grapefruit juice on the pharmacokinetics of repaglinide. Br J Clin Pharmacol 2006 Jan; 61(1): 49–57PubMedCrossRefGoogle Scholar
  215. 215.
    Heykants J, Van Peer A, Van de Velde V, et al. The clinical pharmacokinetics of itraconazole: an overview. Mycoses 1989; 32 Suppl. 1: 67–87PubMedCrossRefGoogle Scholar
  216. 216.
    Kawakami M, Suzuki K, Ishizuka T, et al. Effect of grapefruit juice on pharmacokinetics of itraconazole in healthy subjects. Int J Clin Pharmacol Ther 1998 Jun; 36(6): 306–8PubMedGoogle Scholar
  217. 217.
    Penzak SR, Gubbins PO, Gurley BJ, et al. Grapefruit juice decreases the systemic availability of itraconazole capsules in healthy volunteers. Ther Drug Monit 1999 Jun; 21(3): 304–9PubMedCrossRefGoogle Scholar
  218. 218.
    Gubbins PO, Gurley BJ, Williams DK, et al. Examining sex-related differences in enteric itraconazole metabolism in healthy adults using grapefruit juice. Eur J Clin Pharmacol 2008 Mar; 64(3): 293–301PubMedCrossRefGoogle Scholar
  219. 219.
    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 Aug; 27(8): 866–71PubMedGoogle Scholar
  220. 220.
    Wanwimolruk S, Chalcroft S, Coville PF, et al. Pharmacokinetics of quinine in young and elderly subjects. Trans R Soc Trop Med Hyg 1991 Nov–Dec; 85(6): 714–7PubMedCrossRefGoogle Scholar
  221. 221.
    Ho PC, Chalcroft SC, Coville PF, et al. Grapefruit juice has no effect on quinine pharmacokinetics. Eur J Clin Pharmacol 1999 Jul; 55(5): 393–8PubMedCrossRefGoogle Scholar
  222. 222.
    Eiermann B, Engel G, Johansson I, et al. The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. Br J Clin Pharmacol 1997; 44(5): 439–46PubMedCrossRefGoogle Scholar
  223. 223.
    Raaska K, Neuvonen PJ. Serum concentrations of clozapine and N-desmethylclozapine are unaffected by the potent CYP3A4 inhibitor itraconazole. Eur J Clin Pharmacol 1998 Apr; 54(2): 167–70PubMedCrossRefGoogle Scholar
  224. 224.
    Vandel S, Netillard C, Perault MC, et al. Plasma levels of clozapine and desmethylclozapine are unaffected by concomitant ingestion of grapefruit juice. Eur J Clin Pharmacol 2000 Jul; 56(4): 347–8PubMedCrossRefGoogle Scholar
  225. 225.
    Ozdemir V, Kalow W, Okey AB, et al. Treatment-resistance to clozapine in association with ultrarapid CYP1A2 activity and the C→A polymorphism in intron 1 of the CYP1A2 gene: effect of grapefruit juice and low-dose fluvoxamine. J Clin Psychopharmacol 2001 Dec; 21(6): 603–7PubMedCrossRefGoogle Scholar
  226. 226.
    Yasui N, Kondo T, Suzuki A, et al. Lack of significant pharmacokinetic interaction between haloperidol and grapefruit juice. Int Clin Psychopharmacol 1999 Mar; 14(2): 113–8PubMedCrossRefGoogle Scholar
  227. 227.
    Demarles D, Gillotin C, Bonaventure-Paci S, et al. Singledose pharmacokinetics of amprenavir coadministered with grapefruit juice. Antimicrob Agents Chemother 2002 May; 46(5): 1589–90PubMedCrossRefGoogle Scholar
  228. 228.
    Telzir (fosamprenavir) tablets: summary of product characteristics. ViiV Healthcare UK Ltd. Updated 19/5/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 12]
  229. 229.
    Chiba M, Hensleigh M, Lin JH. Hepatic and intestinal metabolism of indinavir, an HIV protease inhibitor, in rat and human microsomes: major role of CYP3A. Biochem Pharmacol 1997 Apr 25; 53(8): 1187–95PubMedCrossRefGoogle Scholar
  230. 230.
    Penzak SR, Acosta EP, Turner M, et al. Effect of Seville orange juice and grapefruit juice on indinavir pharmacokinetics. J Clin Pharmacol 2002 Oct; 42(10): 1165–70PubMedCrossRefGoogle Scholar
  231. 231.
    Shelton MJ, Wynn HE, Hewitt RG, et al. Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects. J Clin Pharmacol 2001 Apr; 41(4): 435–42PubMedCrossRefGoogle Scholar
  232. 232.
    Kupferschmidt HH, Fattinger KE, Ha HR, et al. Grapefruit juice enhances the bioavailability of the HIV protease inhibitor saquinavir in man. Br J Clin Pharmacol 1998 Apr; 45(4): 355–9PubMedCrossRefGoogle Scholar
  233. 233.
    Invirase (saquinavir 500mg film-coated tablets): summary of product characteristics. Roche Products Limited. Updated 05/08/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Feb 1]
  234. 234.
    Sustiva (efavirenz 600mg film coated tablets): summary of product characteristics. Bristol-Myers Squibb Pharmaceuticals Ltd. Updated 07/09/2009 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Feb 1]
  235. 235.
    Renner UD, Oertel R, Kirch W. Pharmacokinetics and pharmacodynamics in clinical use of scopolamine. Ther Drug Monit 2005 Oct; 27(5): 655–65PubMedCrossRefGoogle Scholar
  236. 236.
    Ebert U, Oertel R, Kirch W. Influence of grapefruit juice on scopolamine pharmacokinetics and pharmacodynamics in healthy male and female subjects. Int J Clin Pharmacol Ther 2000 Nov; 38(11): 523–31PubMedGoogle Scholar
  237. 237.
    Yasui N, Kondo T, Furukori H, et al. Effects of repeated ingestion of grapefruit juice on the single and multiple oral-dose pharmacokinetics and pharmacodynamics of alprazolam. Psychopharmacology (Berl) 2000 Jun; 150(2): 185–90CrossRefGoogle Scholar
  238. 238.
    Lanoxin (digoxin 0.25mg tablets): summary of product characteristics. GlaxoSmithKline UK. Updated 08/03/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Feb 1]
  239. 239.
    Parker RB, Yates CR, Soberman JE, et al. Effects of grapefruit juice on intestinal P-glycoprotein: evaluation using digoxin in humans. Pharmacotherapy 2003 Aug; 23(8): 979–87PubMedCrossRefGoogle Scholar
  240. 240.
    Lilja JJ, Raaska K, Neuvonen PJ. Effects of grapefruit juice on the pharmacokinetics of acebutolol. Br J Clin Pharmacol 2005 Dec; 60(6): 659–63PubMedCrossRefGoogle Scholar
  241. 241.
    Christensen H, Asberg A, Holmboe AB, et al. Coadministration of grapefruit juice increases systemic exposure of diltiazem in healthy volunteers. Eur J Clin Pharmacol 2002 Nov; 58(8): 515–20PubMedCrossRefGoogle Scholar
  242. 242.
    Doppenschmitt S, Spahn-Langguth H, Regardh CG, et al. Role of P-glycoprotein-mediated secretion in absorptive drug permeability: an approach using passive membrane permeability and affinity to P-glycoprotein. J Pharm Sci 1999 Oct; 88(10): 1067–72PubMedCrossRefGoogle Scholar
  243. 243.
    Edgar B, Regardh CG, Johnsson G, et al. Felodipine kinetics in healthy men. Clin Pharmacol Ther 1985 Aug; 38(2): 205–11PubMedCrossRefGoogle Scholar
  244. 244.
    Pisarik P. Blood pressure-lowering effect of adding grapefruit juice to nifedipine and terazosin in a patient with severe renovascular hypertension. Arch Fam Med 1996 Jul–Aug;5(7): 413–6PubMedCrossRefGoogle Scholar
  245. 245.
    Plendil (felodipine) tablets: summary of product characteristics. AstraZeneca UK Ltd. Updated 11/03/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Jul 22]
  246. 246.
    Stearns RA, Chakravarty PK, Chen R, et al. Biotransformation of losartan to its active carboxylic acid metabolite in human liver microsomes: role of cytochrome P4502C and 3A subfamily members. Drug Metab Dispos 1995 Feb; 23(2): 207–15PubMedGoogle Scholar
  247. 247.
    Kaukonen KM, Olkkola KT, Neuvonen PJ. Fluconazole but not itraconazole decreases the metabolism of losartan to E-3174. Eur J Clin Pharmacol 1998 Feb; 53(6): 445–9PubMedCrossRefGoogle Scholar
  248. 248.
    Zaidenstein R, Soback S, Gips M, et al. Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers. Ther Drug Monit 2001 Aug; 23(4): 369–73PubMedCrossRefGoogle Scholar
  249. 249.
    Varis T, Kaukonen KM, Kivisto KT, et al. Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole. Clin Pharmacol Ther 1998 Oct; 64(4): 363–8PubMedCrossRefGoogle Scholar
  250. 250.
    Varis T, Kivisto KT, Neuvonen PJ. Grapefruit juice can increase the plasma concentrations of oral methylprednisolone. Eur J Clin Pharmacol 2000 Sep; 56(6–7): 489–93PubMedCrossRefGoogle Scholar
  251. 251.
    Varis T, Kivisto KT, Backman JT, et al. The cytochrome P450 3A4 inhibitor itraconazole markedly increases the plasma concentrations of dexamethasone and enhances its adrenal-suppressant effect. Clin Pharmacol Ther 2000 Nov; 68(5): 487–94PubMedCrossRefGoogle Scholar
  252. 252.
    Raaska K, Niemi M, Neuvonen M, et al. Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole. Clin Pharmacol Ther 2002 Oct; 72(4): 362–9PubMedCrossRefGoogle Scholar
  253. 253.
    Hande K, Messenger M, Wagner J, et al. Inter- and intrapatient variability in etoposide kinetics with oral and intravenous drug administration. Clin Cancer Res 1999 Oct; 5(10): 2742–7PubMedGoogle Scholar
  254. 254.
    Reif S, Nicolson MC, Bisset D, et al. Effect of grapefruit juice intake on etoposide bioavailability. Eur J Clin Pharmacol 2002 Oct; 58(7): 491–4PubMedCrossRefGoogle Scholar
  255. 255.
    Goldbart A, Press J, Sofer S, et al. Near fatal acute colchicine intoxication in a child: a case report. Eur J Pediatr 2000 Dec; 159(12): 895–7PubMedCrossRefGoogle Scholar
  256. 256.
    Fujiwara K, Adachi H, Nishio T, et al. Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology 2001 May; 142(5): 2005–12PubMedCrossRefGoogle Scholar
  257. 257.
    Kassem NA, Deane R, Segal MB, et al. Thyroxine (T4) transfer from CSF to choroid plexus and ventricular brain regions in rabbit: contributory role of P-glycoprotein and organic anion transporting polypeptides. Brain Res 2007 Nov 21; 1181: 44–50PubMedCrossRefGoogle Scholar
  258. 258.
    Lilja JJ, Laitinen K, Neuvonen PJ. Effects of grapefruit juice on the absorption of levothyroxine. Br J Clin Pharmacol 2005 Sep; 60(3): 337–41PubMedCrossRefGoogle Scholar
  259. 259.
    Schubert W, Cullberg G, Edgar B, et al. Inhibition of 17 beta-estradiol metabolism by grapefruit juice in ovariectomized women. Maturitas 1994 Dec; 20(2–3): 155–63PubMedCrossRefGoogle Scholar
  260. 260.
    Weber A, Jager R, Borner A, et al. Can grapefruit juice influence ethinylestradiol bioavailability? Contraception 1996 Jan; 53(1): 41–7PubMedCrossRefGoogle Scholar
  261. 261.
    Grande LA, Mendez RD, Krug RT, et al. Attention: grapefruit! Lancet 2009 Apr 4; 373(9670): 1222PubMedCrossRefGoogle Scholar
  262. 262.
    Wang JS, DeVane CL. Involvement of CYP3A4, CYP2C8, and CYP2D6 in the metabolism of (R)- and (S)-methadone in vitro. Drug Metab Dispos 2003 Jun; 31(6): 742–7PubMedCrossRefGoogle Scholar
  263. 263.
    Benmebarek M, Devaud C, Gex-Fabry M, et al. Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone. Clin Pharmacol Ther 2004 Jul; 76(1): 55–63PubMedCrossRefGoogle Scholar
  264. 264.
    Methadone solution for injection: summary of product characteristics. Wockhardt UK Ltd. Updated 02/09/2008 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Feb 2]
  265. 265.
    Boolell M, Allen MJ, Ballard SA, et al. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 1996 Jun; 8(2): 47–52PubMedGoogle Scholar
  266. 266.
    Ballard TL, Halaweish FT, Stevermer CL, et al. Naringin does not alter caffeine pharmacokinetics, energy expenditure, or cardiovascular haemodynamics in humans following caffeine consumption. Clin Exp Pharmacol Physiol 2006 Apr; 33(4): 310–4PubMedCrossRefGoogle Scholar
  267. 267.
    Strauch K, Lutz U, Bittner N, et al. Dose-response relationship for the pharmacokinetic interaction of grapefruit juice with dextromethorphan investigated by human urinary metabolite profiles. Food Chem Toxicol 2009 Aug; 47(8): 1928–35PubMedCrossRefGoogle Scholar
  268. 268.
    Di Marco MP, Edwards DJ, Wainer IW, et al. The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A and P-glycoprotein. Life Sci 2002 Jul 26; 71(10): 1149–60PubMedCrossRefGoogle Scholar
  269. 269.
    Hukkanen J, Jacob 3rd P, Benowitz NL. Effect of grapefruit juice on cytochrome P450 2A6 and nicotine renal clearance. Clin Pharmacol Ther 2006 Nov; 80(5): 522–30PubMedCrossRefGoogle Scholar
  270. 270.
    Martin J, editor. British national formulary. 58th ed. London: RPS Publishing, 2009: 720–803, 932–46Google Scholar
  271. 271.
    Grapefruit diet: 12-day grapefruit diet plan [online]. Available from URL: http://www.grapefruit-diet.org [Accessed 2010 Feb 3]
  272. 272.
    Dallas C, Gerbi A, Tenca G, et al. Lipolytic effect of a polyphenolic citrus dry extract of red orange, grapefruit, orange (SINETROL) in human body fat adipocytes: mechanism of action by inhibition of cAMP-phosphodiesterase (PDE). Phytomedicine 2008 Oct; 15(10): 783–92PubMedCrossRefGoogle Scholar
  273. 273.
    Greenblatt DJ. Analysis of drug interactions involving fruit beverages and organic anion-transporting polypeptides. J Clin Pharmacol 2009 Dec; 49(12): 1403–7PubMedCrossRefGoogle Scholar
  274. 274.
    Inspra (eplerenone) tablets: summary of product characteristics. Pfizer Limited. Updated 19/11/2009 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Sep 28]
  275. 275.
    Xarelto (rivaroxaban) 10mg tablets: summary of product characteristics. Bayer plc. Updated 30/06/2010 [online]. Available from URL: http://www.medicines.org.uk [Accessed 2010 Sep 28]

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Kay Seden
    • 1
    • 2
    • 3
  • Laura Dickinson
    • 1
    • 2
  • Saye Khoo
    • 2
  • David Back
    • 2
  1. 1.NIHR Biomedical Research CentreRoyal Liverpool and Broadgreen University Hospital TrustLiverpoolUK
  2. 2.Department of PharmacologyUniversity of LiverpoolLiverpoolUK
  3. 3.Pharmacy DepartmentRoyal Liverpool University HospitalLiverpoolUK

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