American Journal of Cardiovascular Drugs

, Volume 4, Issue 5, pp 281–297 | Cite as

Interactions Between Grapefruit Juice and Cardiovascular Drugs

  • Dr David G. BaileyEmail author
  • George K. Dresser
Review Article


Grapefruit juice can alter oral drug pharmacokinetics by different mechanisms. Irreversible inactivation of intestinal cytochrome P450 (CYP) 3A4 is produced by commercial grapefruit juice given as a single normal amount (e. g. 200–300mL) or by whole fresh fruit segments. As a result, presystemic metabolism is reduced and oral drug bioavailability increased. Enhanced oral drug bioavailability can occur 24 hours after juice consumption. Inhibition of P-glycoprotein (P-gp) is a possible mechanism that increases oral drug bioavailability by reducing intestinal and/or hepatic efflux transport. Recently, inhibition of organic anion transporting polypeptides by grapefruit juice was observed in vitro; intestinal uptake transport appeared decreased as oral drug bioavailability was reduced.

Numerous medications used in the prevention or treatment of coronary artery disease and its complications have been observed or are predicted to interact with grapefruit juice. Such interactions may increase the risk of rhabdomyolysis when dyslipidemia is treated with the HMG-CoA reductase inhibitors atorvastatin, lovastatin, or simvastatin. Potential alternative agents are pravastatin, fluvastatin, or rosuvastatin. Such interactions might also cause excessive vasodilatation when hypertension is managed with the dihydropyridines felodipine, nicardipine, nifedipine, nisoldipine, or nitrendipine. An alternative agent could be amlodipine. In contrast, the therapeutic effect of the angiotensin II type 1 receptor antagonist losartan may be reduced by grapefruit juice. Grapefruit juice interacting with the antidiabetic agent repaglinide may cause hypoglycemia, and interaction with the appetite suppressant sibutramine may cause elevated BP and HR. In angina pectoris, administration of grapefruit juice could result in atrioventricular conduction disorders with verapamil or attenuated antiplatelet activity with clopidrogel. Grapefruit juice may enhance drug toxicity for antiarrhythmic agents such as amiodarone, quinidine, disopyramide, or propafenone, and for the congestive heart failure drug, carvediol.

Some drugs for the treatment of peripheral or central vascular disease also have the potential to interact with grapefruit juice. Interaction with sildenafil, tadalafil, or vardenafil for erectile dysfunction, may cause serious systemic vasodilatation especially when combined with a nitrate. Interaction between ergotamine for migraine and grapefruit juice may cause gangrene or stroke. In stroke, interaction with nimodipine may cause systemic hypotension.

If a drug has low inherent oral bioavailability from presystemic metabolism by CYP3A4 or efflux transport by P-gp and the potential to produce serious overdose toxicity, avoidance of grapefruit juice entirely during pharmacotherapy appears mandatory. Although altered drug response is variable among individuals, the outcome is difficult to predict and avoiding the combination will guarantee toxicity is prevented. The elderly are at particular risk, as they are often prescribed medications and frequently consume grapefruit juice.


Amiodarone Felodipine Disopyramide Telmisartan Propafenone 
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.


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  1. 1.
    Bailey DG, Spence JD, Munoz C, et al. Interaction of citrus juices with felodipine and nifedipine. Lancet 1991; 337: 268–9PubMedGoogle Scholar
  2. 2.
    Bailey DG, Arnold JMO, Spence JD. Grapefruit juice and drugs: how significant is the interaction? Clin Pharmacokinet 1994; 26: 91–8PubMedGoogle Scholar
  3. 3.
    Ameer B, Weintraub RA. Drug interactions with grapefruit juice. Clin Pharmacokinet 1997; 33: 103–21PubMedGoogle Scholar
  4. 4.
    Fuhr U. Drug interactions with grapefruit juice: extent, probable mechanism of action and clinical relevance. Drug Saf 1998; 18: 251–72PubMedGoogle Scholar
  5. 5.
    Bailey DG, Arnold JMO, Spence JD. Grapefruit juice-drug interactions. Br J Clin Pharmacol 1998; 46: 101–10PubMedGoogle Scholar
  6. 6.
    Guengerich FP. Cytochrome P-450 3A4: regulation and role in drug metabolism. Annu Rev Pharmacol Toxicol 1999; 39: 1–17PubMedGoogle Scholar
  7. 7.
    Kolars JC, Schmiedlin-Rem P, Schuetz JD, et al. Identification of rifampicin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes. J Clin Invest 1992; 90: 1871–8PubMedGoogle Scholar
  8. 8.
    Lown KS, Kolars JC, Thummel KE, et al. Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel: lack of prediction by the erythromycin breath test. Drug Metab Dispos 1994; 22: 947–55PubMedGoogle Scholar
  9. 9.
    Edgar B, Regardh CG, Johnsson G, et al. Felodipine kinetics in healthy man. Clin Pharmacol Ther 1985; 38: 205–11PubMedGoogle Scholar
  10. 10.
    Blychert E, Edgar B, Elmfeldt D, et al. A population study of the pharmacokinetics of felodipine. Br J Clin Pharmacol 1991; 31: 15–24PubMedGoogle Scholar
  11. 11.
    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; 99: 2545–53PubMedGoogle Scholar
  12. 12.
    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: 61–7PubMedGoogle Scholar
  13. 13.
    Takanaga H, Ohnishi A, Murakami H, et al. Relationship between time after intake of grapefruit juice and the effect on the pharmacokinetics and pharmacodynamics of nisoldipine in healthy subjects. Clin Pharmacol Ther 2000; 67: 201–14PubMedGoogle Scholar
  14. 14.
    Lilja JJ, Kivisto KT, Neuvonen PJ. Duration of effect of grapefruit juice on the pharmacokinetics of the CYP3A4 substrate simvastatin. Clin Pharmacol Ther 2000; 68: 384–90PubMedGoogle Scholar
  15. 15.
    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: 139–45PubMedGoogle Scholar
  16. 16.
    Ducharme MP, Warbasse LH, Edwards DJ. Disposition of intravenous and oral cyclosporine after administration with grapefruit juice. Clin Pharmacol Ther 1995; 57: 485–91PubMedGoogle Scholar
  17. 17.
    Bailey DG, Dresser GK, Kreeft JH, et al. Grapefruit-felodipine interaction: effect of unprocessed fruit and probable active ingredients. Clin Pharmacol Ther 2000; 68: 468–77PubMedGoogle Scholar
  18. 18.
    Edgar B, Bailey DG, Bergstrand R, et al. Acute effects of drinking grapefruit juice on the pharmacokinetics and pharmacodynamics of felodipine: and its potential clinical relevance. Eur J Clin Pharmacol 1992; 42: 313–7PubMedGoogle Scholar
  19. 19.
    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; 56: 411–5PubMedGoogle Scholar
  20. 20.
    Bailey DG, Arnold JMO, Bend JR, et al. Grapefruit juice-felodipine interaction: reproducibility and characterization with the extended release drug formulation. Br J Clin Pharmacol 1995; 40: 135–40PubMedGoogle Scholar
  21. 21.
    Bailey DG, Arnold JMO, Munoz C, et al. Grapefruit juice-felodipine interaction: mechanism, predictability and effect of naringin. Clin Pharmacol Ther 1993; 53: 637–42PubMedGoogle Scholar
  22. 22.
    Kim RB. Transporters and drug disposition. Curr Opin Drug Discov Dev 2000; 3: 94–101Google Scholar
  23. 23.
    Lin JH, Yazamaki M. Role of P-glycoprotein in pharmacokinetics: clinical implications [review]. Clin Pharmacokinet 2003; 42: 59–98PubMedGoogle Scholar
  24. 24.
    Malhotra S, Bailey DG, Paine MF, et al. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of the furanocoumarins. Clin Pharmacol Ther 2001; 69: 14–23PubMedGoogle Scholar
  25. 25.
    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; 65: 237–44PubMedGoogle Scholar
  26. 26.
    Becquemont L, Verstuyft C, Kerb R, et al. Effect of grapefruit juice on digoxin pharmacokinetics in humans. Clin Pharmacol Ther 2001; 70: 311–6PubMedGoogle Scholar
  27. 27.
    Spahn-Langguth H, Langguth P. Grapefruit juice enhances intestinal absorption of the P-glycoprotein substrate talinolol. Eur J Pharm Sci 2001; 12: 316–7Google Scholar
  28. 28.
    Tian R, Koyabu N, Takanaga H, et al. Effects of grapefruit on the intestinal efflux of P-glycoprotein substrates. Pharm Res 2002; 19: 802–9PubMedGoogle Scholar
  29. 29.
    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; 21: 1062–6PubMedGoogle Scholar
  30. 30.
    Soldner A, Christians U, Susanto M, et al. Grapefruit juice activates P-glycoprotein-mediated drug transport. Pharm Res 1999; 16: 478–85PubMedGoogle Scholar
  31. 31.
    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; 71: 11–20PubMedGoogle Scholar
  32. 32.
    Lea AP, McTavish D. Atorvastatin: a review of its pharmacology and therapeutic potential in the management of hyperlipidaemias. Drugs 1997; 53: 828–47PubMedGoogle Scholar
  33. 33.
    Kantola T, Kivisto KT, Neuvonen PJ. Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther 1998; 63: 397–402PubMedGoogle Scholar
  34. 34.
    Vickers S, Duncan CA, Chen IW, et al. Metabolic disposition studies on simvastatin, a cholesterol-lowering prodrug. Drug Metab Dispos 1990; 18: 138–45PubMedGoogle Scholar
  35. 35.
    Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin Pharmacol Ther 1999; 66: 118–27PubMedGoogle Scholar
  36. 36.
    Rogers JD, Zhao J, Liu L, et al. Grapefruit juice has minimal effects on plasma concentrations of lovastatin-derived 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Clin Pharmacol Ther 1999; 66: 358–66PubMedGoogle Scholar
  37. 37.
    Bailey DG, Dresser GK. Grapefruit juice: lovastatin interaction [letter]. Clin Pharmacol Ther 2000; 67: 690PubMedGoogle Scholar
  38. 38.
    Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice-simvastatin interaction: effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Clin Pharmacol Ther 1998; 64: 477–83PubMedGoogle Scholar
  39. 39.
    Dreier JP, Endres M. Statin-associated rhabdomyolysis triggered by grapefruit consumption. Neurology 2004; 62(4): 670PubMedGoogle Scholar
  40. 40.
    Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet 2000; 38: 41–57PubMedGoogle Scholar
  41. 41.
    Cooper KJ, Martin PD, Dane AL, et al. Lack of effect of ketoconazole on the pharmacokinetics of rosuvastatin in healthy subjects. Br J Clin Pharmacol 2003; 55: 94–9PubMedGoogle Scholar
  42. 42.
    Bailey DG, Kreeft JH, Munoz C, et al. Grapefruit juice-felodipine interaction: effect of naringin and 6’,7’-dihydroxybergamottin in humans. Clin Pharmacol Ther 1998; 64: 248–56PubMedGoogle Scholar
  43. 43.
    Dresser GK, Bailey DG, Carruthers SG. Grapefruit juice-felodipine interaction in the elderly. Clin Pharmacol Ther 2000; 68: 28–34PubMedGoogle Scholar
  44. 44.
    Bailey DG, Bend JR, Arnold JMO, et al. Erythromycin-felodipine interaction: magnitude, mechanism, and comparison with grapefruit juice. Clin Pharmacol Ther 1996; 60: 25–33PubMedGoogle Scholar
  45. 45.
    Laitinen T, Hartikainen J, Vanninen E, et al. Age and gender dependency of sensitivity in healthy subjects. J Appl Physiol 1998; 84: 576–83PubMedGoogle Scholar
  46. 46.
    Landahl S, Edgar B, Gabrielsson M, et al. Pharmacokinetics and blood pressure effects of felodipine in elderly hypertensive patients: a comparison with young healthy subjects. Clin Pharmacokinet 1998; 14: 374–83Google Scholar
  47. 47.
    Uno T, Ohkubo T, Sugawara K, et al. Effect 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; 56: 643–9PubMedGoogle Scholar
  48. 48.
    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; 36: 460–3PubMedGoogle Scholar
  49. 49.
    Rashid TJ, Martin U, Clarke H, et al. Factors affecting the absolute bioavailability of nifedipine. Br J Clin Pharmacol 1995; 40: 51–8PubMedGoogle Scholar
  50. 50.
    Sigusch H, Hippius M, Henschel L, et al. Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation. Pharmazie 1994; 49: 522–4PubMedGoogle Scholar
  51. 51.
    Bailey DG, Arnold JMO, Strong HA, et al. Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics. Clin Pharmacol Ther 1993; 54: 589–94PubMedGoogle Scholar
  52. 52.
    Soons PA, Vogels BAPM, Roosemalen MCM, et al. Grapefruit juice and cimetidine inhibit stereoselective metabolism of nitrendipine in man. Clin Pharmacol Ther 1991; 50: 394–403PubMedGoogle Scholar
  53. 53.
    Bailey DG, Munoz C, Arnold JMO, et al. Grapefruit juice and naringin interaction with nitrendipine [abstract]. Clin Pharmacol Ther 1992; 51: 156Google Scholar
  54. 54.
    Josefsson M, Zackrisson AL, Ahlner J. Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers. Eur J Clin Pharmacol 1996; 51: 189–93PubMedGoogle Scholar
  55. 55.
    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; 50: 455–63PubMedGoogle Scholar
  56. 56.
    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; 23: 369–73PubMedGoogle Scholar
  57. 57.
    Atacand® (candesartin cilexetil). Product monograph. Mississauga, Ontario: AstraZeneca Canada Inc., 2004Google Scholar
  58. 58.
    Teveten® (eprosartin mesylate). Product monograph. Markham, Ontario: Solvay Pharma Inc., 2004Google Scholar
  59. 59.
    Micardis® (telmisartan). Product monograph. Burlington, Ontario: Boehringer Ingelheim Canada Ltd. 2003Google Scholar
  60. 60.
    Diovan® (valsartan). Product monograph. Corval, Quebec: Novartis Pharmaceuticals Canada Inc., 2002Google Scholar
  61. 61.
    Stangier J, Su CA, Hendrick MG, et al. The effect of telmisartan on the steady state pharmacokinetics of digoxin in healthy male volunteers. J Clin Pharmacol 2000; 40: 1373–9PubMedGoogle Scholar
  62. 62.
    Weber MA. Vasopeptidase inhibitors. Lancet 2001; 358: 1525–32PubMedGoogle Scholar
  63. 63.
    Malhotra BK, Iyer RA, Soucek KM, et al. Oral bioavailability and disposition of [14C]omapatrilat in healthy subjects. J Clin Pharmacol 2001; 41: 833–41PubMedGoogle Scholar
  64. 64.
    Iyer RA, Malhotra B, Khan S, et al. Comparative biotransformation of radiolabeled [(14)C]omapatrilat and stable-labeled [(13)C(2)]omapatrilat after oral administration to rats, dogs, and humans. Drug Metab Dispos 2003; 31: 67–75PubMedGoogle Scholar
  65. 65.
    Niemi M, Neuvonen PJ, Kivisto KT. The cytochrome P4503A4 inhibitor clarithromycin increases the plasma concentrations and effects of repaglinide. Clin Pharmacol Ther 2001; 70: 58–65PubMedGoogle Scholar
  66. 66.
    Hanefeld M. Pharmacokinetics and clinical efficacy of pioglitazone. Int J Clin Pract Suppl 2001; 121: 19–25PubMedGoogle Scholar
  67. 67.
    Avandia® (rosiglitazone maleate). Product monograph. Mississauga, Ontario: GlaxoSmithKline Inc., 2004Google Scholar
  68. 68.
    Meridia® (sibutramine). Product monograph. Saint-Laurent, Quebec: Abbott Laboratories Ltd. 2002Google Scholar
  69. 69.
    Sigusch H, Henschel L, Kraul H, et al. Lack of effect of grapefruit juice on diltiazem bioavailability in normal subjects. Pharmazie 1994; 49: 675–9PubMedGoogle Scholar
  70. 70.
    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; 58: 515–20PubMedGoogle Scholar
  71. 71.
    Isoptin® (verapamil). Product monograph. Saint-Laurent, Quebec: Abbott Laboratories Ltd., 2004Google Scholar
  72. 72.
    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; 54: 337–40PubMedGoogle Scholar
  73. 73.
    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; 56: 693–8PubMedGoogle Scholar
  74. 74.
    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; 58: 45–53PubMedGoogle Scholar
  75. 75.
    Lau WC, Waskell LA, Watkins PB, et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation 2003; 107: 32–7PubMedGoogle Scholar
  76. 76.
    Freedman MD, Somberg JC. Pharmacology and pharmacokinetics of amiodarone. J Clin Pharmacol 1991; 31: 1061–9PubMedGoogle Scholar
  77. 77.
    Fabre G, Julian B, Saint-Auber B, et al. Evidence of CYP3A-mediated N-deethylation of amiodarone in human liver microsomal fractions. Drug Metab Dispos 1993; 21: 978–85PubMedGoogle Scholar
  78. 78.
    Libersa CC, Brique SA, Motte KB, et al. Dramatic inhibition of amiodarone metabolism induced by grapefruit juice. Br J Clin Pharmacol 2000; 49: 373–8PubMedGoogle Scholar
  79. 79.
    Guentert TW, Holford N, Coates PE, et al. Quinidine pharmacokinetics in man: choice of a disposition model and absolute bioavailability studies. J Pharmacokinet Biopharm 1979; 7: 315–30PubMedGoogle Scholar
  80. 80.
    Kessler KM, Lowenthal DT, Warner H, et al. Quinidine elimination in patients with congestive heart failure or poor renal function. N Engl J Med 1974; 290: 706–9PubMedGoogle Scholar
  81. 81.
    Min DI, Ku YM, Geraets DR, et al. Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers. J Clin Pharmacol 1996; 36: 469–76PubMedGoogle Scholar
  82. 82.
    Damkier P, Hansen LL, Brosen K. Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine. Br J Clin Pharmacol 1999; 48: 829–38PubMedGoogle Scholar
  83. 83.
    Ragosta M, Weihl AC, Rosenfeld LE. Potentially fatal interaction between erythromycin and disopyramide. Am J Med 1989; 864: 465–6Google Scholar
  84. 84.
    Paar D, Terjung B, Sauerbruch T. Life-threatening interaction between clarithromycin and disopyramide. Lancet 1997; 349: 326–7PubMedGoogle Scholar
  85. 85.
    Hayashi Y, Ikeda U, Hashimoto T, et al. Torsades de pointes ventricular tachycardia induced by clarithromycin and disopyramide in the presence of hypokalemia. Pacing Clin Electrophysiol 1999; 22: 672–4PubMedGoogle Scholar
  86. 86.
    Braun J, Sorgel F, Gluth WP, et al. Bioavailability of disopyramide in normal volunteers using unbound concentration. Eur J Clin Pharmacol 1987; 32: 625–9PubMedGoogle Scholar
  87. 87.
    Rythmol® (propafenone). Product monograph. Saint-Laurent, Quebec: Abbott Laboratories Ltd., 2004Google Scholar
  88. 88.
    Munoz CE, Ito S, Bend JR, et al. Propafenone interaction with CYP3A4 inhibitors in man [abstract]. Clin Pharmacol Ther 1997; 61: 154Google Scholar
  89. 89.
    Duvelleroy Hommet C, Jonville-Bera AP, Autret A, et al. Convulsive seizures in a patient treated with propafenone and ketoconazole. Therapie 1995; 50: 164–5PubMedGoogle Scholar
  90. 90.
    Breckenridge A, Orme M, Wessling H, et al. Pharmacokinetics and pharmacodynamics of the enantiomers of warfarin in man. Clin Pharmacol Ther 1974; 15: 424–30PubMedGoogle Scholar
  91. 91.
    Miners JO, Birkett DJ. Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol 1998; 45: 525–38PubMedGoogle Scholar
  92. 92.
    Schwartz J, Bachmann K, Perrigo E. Interaction between warfarin and erythromycin. South Med J 1983; 76: 91–3PubMedGoogle Scholar
  93. 93.
    Recker MW, Kier KL. Potential interaction between clarithromycin and warfarin. Ann Pharmacother 1997; 31: 996–8PubMedGoogle Scholar
  94. 94.
    Smith AG. Potentiation of oral anticoagulant effects by ketoconazole. BMJ 1984; 288: 188–9PubMedGoogle Scholar
  95. 95.
    Yeh J, Soo SC, Summerton C, et al. Potentiation of action of warfarin by itraconazole [letter]. BMJ 1990; 301: 669PubMedGoogle Scholar
  96. 96.
    Kates RE, Yee Y-G, Kirsten EB. Interaction between warfarin and propafenone in healthy volunteer subjects. Clin Pharmacol Ther 1987; 42: 305–11PubMedGoogle Scholar
  97. 97.
    Sullivan DM, Ford MA, Boyden TW. Grapefruit juice and the response to warfarin. Am J Health Syst Pharm 1998; 55: 1581–3PubMedGoogle Scholar
  98. 98.
    Dresser GK, Munoz C, Cruikshank M, et al. Grapefruit juice-warfarin interaction in anticoagulated patients [abstract]. Clin Pharmacol Ther 1999; 65: 193Google Scholar
  99. 99.
    van Rooij J, van der Meer FJM, 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: 548PGoogle Scholar
  100. 100.
    Wakasugi H, Yano I, Ito T, et al. Effect of clarithromycin on renal excretion of digoxin: interaction with P-glycoprotein. Clin Pharmacol Ther 1998; 64: 123–8PubMedGoogle Scholar
  101. 101.
    Fromm MF, Kim RB, Stein CM, et al. Inhibition of P-glycoprotein-mediated drug transport: a unifying mechanism to explain the interaction between digoxin and quinidine. Circulation 1999; 99: 552–7PubMedGoogle Scholar
  102. 102.
    Verschraagen M, Koks CHW, Schellens JHM, et al. P-glycoprotein system as a determinant of drug interactions: the case of digoxin-verapamil. Pharmacol Res 1999; 40: 301–6PubMedGoogle Scholar
  103. 103.
    Fenster PE, White NW, Hanson CD. Pharmacokinetic evaluation of the digoxinamiodarone interaction. J Am Coll Cardiol 1985; 5: 108–12PubMedGoogle Scholar
  104. 104.
    Partanen J, Jalava KM, Neuvonen PJ. Itraconazole increases serum digoxin concentrations. Pharmacol Toxicol 1996; 79: 274–6PubMedGoogle Scholar
  105. 105.
    Jalava KM, Partanen J, Neuvonen PJ. Itraconazole decreases renal clearance of digoxin. Ther Drug Monit 1997; 19: 609–13PubMedGoogle Scholar
  106. 106.
    Coreg® (carvedilol). Product monograph. Mississauga, Ontario: GlaxoSmithKline Inc., 2004Google Scholar
  107. 107.
    Walker DK, Ackland MJ, James GC, et al. Pharmacokinetics and metabolism of sildenafil in mouse, rat, rabbit, dog and man. Xenobiotica 1999; 29: 297–310PubMedGoogle Scholar
  108. 108.
    Warrington JS, Shader RI, von Moltke LL, et al. In vitro biotransformations of sildenafil (Viagra): identification of human cytochromes and potential drug interactions. Drug Metab Dispos 2000; 28: 392–7PubMedGoogle Scholar
  109. 109.
    Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. Effects of grapefruit juice on the pharmacokinetics of sildenafil. Clin Pharmacol Ther 2002; 71: 21–9PubMedGoogle Scholar
  110. 110.
    Sanders SW, Haering N, Mosberg H, et al. Pharmacokinetics of ergotamine in healthy volunteers following oral and rectal dosing. Eur J Clin Pharmacol 1986; 30: 331–4PubMedGoogle Scholar
  111. 111.
    Health Canada, Health Products and Food Branch, Ottawa, Ontario. New contraindications for medications containing ergotamine and dihydroergotamine [online]. Available at URL: [Accessed 2004 Jun 8]
  112. 112.
    Fuhr U, Maier-Bruggemann A, Blume H, et al. Grapefruit juice increases oral nimodipine bioavailability. Int J Clin Pharmacol Ther 1998; 36: 126–32PubMedGoogle Scholar

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© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Department of Medicine and Lawson Health Research InstituteLondon Health Sciences CentreLondonCanada
  2. 2.Department of Physiology & PharmacologyUniversity of Western OntarioLondonCanada

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