Food-drug interaction: Grapefruit juice augments drug bioavailability - Mechnism, extent and relevance

European Journal of Clinical Nutrition

Volumn 58, Issue 1, 2004, Pages 1-9

  Dahan, A ^a   Altman, H ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

Bioavailability; Cytochrome P 450 3A4; Drug interaction; Grapefruit; P glycoprotein; Pharmacokinetics

Indexed keywords

AMIODARONE; AMLODIPINE; ATORVASTATIN; BENZODIAZEPINE DERIVATIVE; BUSPIRONE; CALCIUM CHANNEL BLOCKING AGENT; CARBAMAZEPINE; CARRIER PROTEIN; CISAPRIDE; CYCLOSPORIN; CYTOCHROME P450 3A4; DIAZEPAM; FELODIPINE; GLYCOPROTEIN P; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; MEVINOLIN; MIDAZOLAM; NIFEDIPINE; NIMODIPINE; NISOLDIPINE; NITRENDIPINE; PRANIDIPINE; SAQUINAVIR; SERTRALINE; SILDENAFIL; SIMVASTATIN; TERFENADINE; TRIAZOLAM; UNINDEXED DRUG; VERAPAMIL;

ACUTE KIDNEY FAILURE; BRAIN DISEASE; CENTRAL NERVOUS SYSTEM DEPRESSION; CONTROLLED STUDY; DRUG ABSORPTION; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG MECHANISM; DRUG METABOLISM; DRUG TRANSPORT; ENZYME INHIBITION; EXPOSURE; FOOD DRUG INTERACTION; GRAPEFRUIT JUICE; HEART ARRHYTHMIA; HEART MUSCLE CONDUCTION DISTURBANCE; HUMAN; HYPERTENSION; HYPOTENSION; INHIBITION KINETICS; INTESTINE CELL; KIDNEY DISEASE; REVIEW; RHABDOMYOLYSIS; SIDE EFFECT; SMALL INTESTINE; TACHYCARDIA; TORSADE DES POINTES;

BEVERAGES; BIOLOGICAL AVAILABILITY; CALCIUM CHANNEL BLOCKERS; CENTRAL NERVOUS SYSTEM AGENTS; CITRUS PARADISI; CYTOCHROME P-450 ENZYME SYSTEM; FOOD-DRUG INTERACTIONS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; INTESTINAL ABSORPTION; P-GLYCOPROTEIN; PHARMACOKINETICS;

CITRUS X PARADISI;

EID: 0742289647     PISSN: 09543007     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.ejcn.1601736     Document Type: Review

References (94)

1. Bailey DG, Arnold JM, Bend JR, Tran LT & Spence JD (1995): Grapefruit juice-felodipine interaction: reproducibility and characterization with the extended release drug formulation. Br. J. Clin. Pharmacol. 40, 135-140.
2. Bailey DG, Arnold JM, Munoz C & Spence JD (1993a): Grapefruit juice-felodipine interaction: mechanism, predictability, and effect of naringin. Clin. Pharmacol. Ther. 53, 637-642.
3. Bailey DG, Arnold JM, Strong HA, Munoz C & Spence JD (1993b): Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics. Clin. Pharmacol. Ther. 54, 589-594.
4. Bailey DG, Dresser GK, Kreeft JH, Munoz C, Freeman DJ & Bend JR (2000): Grapefruit-felodipine interaction: effect of unprocessed fruit and probable active ingredients. Clin. Pharmacol. Ther. 68, 468-477.
5. Bailey DG, Malcolm J, Arnold O & Spence JD (1998): Grapefruit juice-drug interactions. Br. J. Clin. Pharmacol. 46, 101-110.
6. Bailey DG, Spence JD, Edgar B, Bayliff CD & Arnold JM (1989): Ethanol enhances the hemodynamic effects of felodipine. Clin. Invest. Med. 12, 357-362.
7. Bailey DG, Spence JD, Munoz C & Arnold JM (1991): Interaction of citrus juices with felodipine and nifedipine. Lancet 337, 268-269.
8. Benton RE, Honig PK, Zamani K, Cantilena LR & Woosley RL (1996): Grapefruit juice alters terfenadine pharmacokinetics, resulting in prolongation of repolarization on the electrocardiogram. Clin. Pharmacol. Ther. 59, 383-388.
9. Bistrup C, Nielsen FT, Jeppesen UE & Dieperink H (2001): Effect of grapefruit juice on sandimmun neoral absorption among stable renal allograft recipients. Nephrol. Dial. Transplant 16, 373-377.
10. Bohets H, Lavrijsen K, Hendrickx J, van Houdt J, van Genechten V, Verboven P, Meuldermans W & Heykants J (2000): Identification of the cytochrome P450 enzymes involved in the metabolism of cisapride: in vitro studies of potential co-medication interactions. Br. J. Pharmacol. 129, 1655-1667.
11. Brunner LJ, Pai KS, Munar MY, Lande MB, Olyaei AJ & Mowry JA (2000): Effect of grapefruit juice on cyclosporin A pharmacokinetics in pediatric renal transplant patients. Pediatr. Transplant. 4, 313-321.
12. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR & Davies DS (1997): The cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice. Eur. J. Clin. Pharmacol. 52, 311-315.
13. Dresser GK, Bailey DG & Carruthers SG (2000): Grapefruit juice-felodipine interaction in the elderly. Clin. Pharmacol. Ther. 68, 28-34.
14. Ducharme MP, Warbasse LH & Edwards DJ (1995): Disposition of intravenous and oral cyclosporine after administration with grapefruit juice. Clin. Pharmacol. Ther. 57, 485-491.
15. Eagling VA, Profit L & Back DJ (1999): Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components. Br. J. Clin. Pharmacol. 48, 543-552.
16. Edgar B, Bailey D, Bergstrand R, Johnsson G & Regardh CG (1992): Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine - and its potential clinical relevance. Eur. J. Clin. Pharmacol. 42, 313-317.
17. Edwards DJ, Bellevue III FH & Woster PM (1996): Identification of 6′,7′-dihydroxybergamottin, a cytochrome P450 inhibitor, in grapefruit juice. Drug Metab. Dispos. 24, 1287-1290.
18. Edwards DJ & Bernier SM (1996): Naringin and naringenin are not the primary CYP3A inhibitors in grapefruit juice. Life Sci. 59, 1025-1030.
19. Fabre G, Julian B, Saint Aubert B, Joyeux H & Berger Y (1993): Evidence for CYP3A-mediated N-deethylation of amiodarone in human liver microsomal fractions. Drug Metab. Dispos. 21, 978-985.
20. Fitzsimmons ME & Collins JM (1997): Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome P4503A4: potential contribution to high first-pass metabolism. Drug Metab. Dispos. 25, 256-266.
21. Fuhr U, Maier Bruggemann A, Blume H, Muck W, Unger S, Kuhlmann J, Huschka C, Zaigler M, Rietbrock S & Staib AH (1998): Grapefruit juice increases oral nimodipine bioavailability. Int. J. Clin. Pharmacol. Ther. 36, 126-132.
22. Fuhr U, Muller-Peltzer H, Kern R, Lopez-Rojas F, Junemann M, Harder S & Staib A (2002): Effects of grapefruit juice and smoking on verapamil concentrations in steady state. Eur. J. Clin. Pharmacol. 58, 45-53.
23. Fukuda K, Guo L, Ohashi N, Yoshikawa M & Yamazoe Y (2000): Amounts and variation in grapefruit juice of the main components causing grapefruit-drug interaction. J. Chromatogr. B 741, 195-203.
24. Garg SK, Kumar N, Bhargava VK & Prabhakar SK (1998): Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy. Clin. Pharmacol. Ther. 64, 286-288.
25. Gottesman MM, Pastan I & Ambudkar SV (1996): P-glycoprotein and multidrug resistance. Curr. Opin. Genet. Dev. 6, 610-617.
26. Gross AS, Gob YD, Addison RS & Shenfield GM (1999): Influence of grapefruit juice on cisapride pharmacokinetics. Clin. Pharmacol. Ther. 65, 395-401.
27. Guo LQ, Fukuda K, Ohta T & Yamazoe Y (2000): Role of furanocoumarin derivatives on grapefruit juice-mediated inhibition of human CYP3A activity. Drug Metab. Dispos. 28, 766-771.
28. Hashimoto K, Shirafuji T, Sekino H, Matsuoka O, Onnagawa O, Okamoto T, Kudo S & Azuma J (1998): Interaction of citrus juices with pranidipine, a new 1,4-dihydropyridine calcium antagonist, in healthy subjects. Eur. J. Clin. Pharmacol. 54, 753-760.
29. He K, Iyer KR, Hayes RN, Sinz MW, Woolf TF & Hollenberg PF (1998): Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice. Chem. Res. Toxicol. 11, 252-259.
30. Ho PC, Ghose K, Saville D & Wanwimolruk S (2000): Effect of grapefruit juice on pharmacokinetics and pharmacodynamics of verapamil enantiomers in healthy volunteers. Eur. J. Clin. Pharmacol. 56, 693-698.
31. Honig PK, Wortham DC, Lazarev A & Cantilena LR (1996): Grapefruit juice alters the systemic bioavailability and cardiac repolarization of terfenadine in poor metabolizers of terfenadine. J. Clin. Pharmacol. 36, 345-351.
32. Hukkinen SK, Varhe A, Olkkola KT & Neuvonen PJ (1995): Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice. Clin. Pharmacol. Ther. 58, 127-131.
33. Hyland R, Roe EG, Jones BC & Smith DA (2001): Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil. Br. J. Clin. Pharmacol. 51, 239-248.
34. Ioannides Demos LL, Christophidis N, Ryan P, Angelis P, Liolios L & McLean AJ (1997): Dosing implications of a clinical interaction between grapefruit juice and cyclosporine and metabolite concentrations in patients with autoimmune diseases. J. Rheumatol. 24, 49-54.
35. Jacobsen W, Kirchner G, Hallensleben K, Mancinelli L, Deters M, Hackbarth I, Benet LZ, Sewing KF & Christians U (1999): Comparison of cytochrome P-450-dependent metabolism and drug interactions of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in the liver. Drug Metab. Dispos. 27, 173-179.
36. Jetter A, Kinzig Schippers M, Walchner Bonjean M, Hering U, Bulitta J, Schreiner P, Sorgel F & Fuhr U (2002): Effects of grapefruit juice on the pharmacokinetics of sildenafil. Clin. Pharmacol. Ther. 71, 21-29.
37. Josefsson M, Zackrisson AL & Ahlner J (1996): Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers. Eur. J. Clin. Pharmacol. 51, 189-193.
38. Kane GC & Lipsky JJ (2000): Drug-grapefruit juice interactions. Mayo Clin. Proc. 75, 933-942.
39. Kantola T, Kivisto KT & Neuvonen PJ (1998): Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. Clin. Pharmacol. Ther. 63, 397-402.
40. Kivisto KT, Lilja JJ, Backman JT & Neuvonen PJ (1999): Repeated consumption of grapefruit juice considerably increases plasma concentrations of cisapride. Clin. Pharmacol. Ther. 66, 448-453.
41. Kolars JC, Awni WM, Merion RM & Watkins PB (1991): First-pass metabolism of cyclosporin by the gut. Lancet 338, 1488-1490.
42. Kolars JC, Schmiedlin Ren P, Schuetz JD, Fang C & Watkins PB (1992): Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes. J. Clin. Invest. 90, 1871-1878.
43. Kuhnau J (1976): The flavonoids. A class of semi-essential food components: their role in human nutrition. World Rev. Nutr. Diet. 24, 117-191.
44. Kupferschmidt HH, Fattinger KE, Ha HR, Follath F & Krahenbuhl S (1998): Grapefruit juice enhances the bioavailability of the HIV protease inhibitor saquinavir in man. Br. J. Clin. Pharmacol. 45, 355-359.
45. Kupferschmidt HH, Ha HR, Ziegler WH, Meier PJ & Krahenbuhl S (1995): Interaction between grapefruit juice and midazolam in humans. Clin. Pharmacol. Ther. 58, 20-28.
46. Lee AJ, Chan WK, Harralson AF, Buffum J & Bui BC (1999): The effects of grapefruit juice on sertraline metabolism: an in vitro and in vivo study. Clin. Ther. 21, 1890-1899.
47. Lee M & Min DI (2001): 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. 23, 21-26.
48. Letteron P, Descatoire V, Larrey D, Tinel M, Geneve J & Pessayre D (1986): Inactivation and induction of cytochrome P-450 by various psoralen derivatives in rats. J. Pharmacol. Exp. Ther. 238, 685-692.
49. Libersa CC, Brique SA, Motte KB, Caron JF, Guedon Moreau LM, Humbert L, Vincent A, Devos P & Lhermitte MA (2000): Dramatic inhibition of amiodarone metabolism induced by grapefruit juice. Br. J. Clin. Pharmacol. 49, 373-378.
50. Lilja JJ, Kivisto KT, Backman JT, Lamberg TS & Neuvonen PJ (1998): Grapefruit juice substantially increases plasma concentrations of buspirone. Clin. Pharmacol. Ther. 64, 655-660.
51. Lilja JJ, Kivisto KT, Backman JT & Neuvonen PJ (2000a): Effect of grapefruit juice dose on grapefruit juice-triazolam interaction: repeated consumption prolongs triazolam half-life. Eur. J. Clin. Pharmacol. 56, 411-415.
52. Lilja JJ, Kivisto KT & Neuvonen PJ (1998): Grapefruit juice-simvastatin interaction: effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Clin. Pharmacol. Ther. 64, 477-483.
53. Lilja JJ, Kivisto KT & Neuvonen PJ (1999): Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin. Pharmacol. Ther. 66, 118-127.
54. Lilja JJ, Kivisto KT & Neuvonen PJ (2000b): Duration of effect of grapefruit juice on the pharmacokinetics of the CYP3A4 substrate simvastatin. Clin. Pharmacol. Ther. 68, 384-390.
55. Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, Brown MB, Guo W & Watkins PB (1997): Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. J. Clin. Invest. 99, 2545-2553.
56. Lown KS, Mayo RR, Leichtman AB, Hsiao HL, Turgeon DK, Schmiedlin Ren P, Brown MB, Guo W, Rossi SJ, Benet LZ & Watkins PB (1997): Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine. Clin. Pharmacol. Ther. 62, 248-260.
57. Lundahl J, Regardh CG, Edgar B & Johnsson G (1995): Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects. Eur. J. Clin. Pharmacol. 49, 61-67.
58. Lundahl J, Regardh CG, Edgar B & Johnsson G (1997): Effects of grapefruit juice ingestion - pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men. Eur. J. Clin. Pharmacol. 52, 139-145.
59. Lundahl JU, Regardh CG, Edgar B & Johnsson G (1998): The interaction effect of grapefruit juice is maximal after the first glass. Eur. J. Clin. Pharmacol. 54, 75-81.
60. Michalets EL & Williams CR (2000): Drug interactions with cisapride: clinical implications. Clin. Pharmacokinet. 39, 49-75.
61. Min DI, Ku YM, Perry PJ, Ukah FO, Ashton K, Martin MF & Hunsicker LG (1996): Effect of grapefruit juice on cyclosporine pharmacokinetics in renal transplant patients. Transplantation 62, 123-125.
62. Miniscalco A, Lundahl J, Regardh CG, Edgar B & Eriksson UG (1992): Inhibition of dihydropyridine metabolism in rat and human liver microsomes by flavonoids found in grapefruit juice. J. Pharmacol. Exp. Ther. 261, 1195-1199.
63. Mohri K & Uesawa Y (2001): Effects of furanocoumarin derivatives in grapefruit juice on nifedipine pharmacokinetics in rats. Pharm. Res. 18, 177-182.
64. Offman EM, Freeman DJ, Dresser GK, Munoz C, Bend JR & Bailey DG (2001): Red wine-cisapride interaction: comparison with grapefruit juice. Clin. Pharmacol. Ther. 70, 17-23.
65. Ohnishi A, Matsuo H, Yamada S, Takanaga H, Morimoto S, Shoyama Y, Ohtani H & Sawada Y (2000): Effect of furanocoumarin derivatives in grapefruit juice on the uptake of vinblastine by Caco-2 cells and on the activity of cytochrome P450 3A4. Br. J. Pharmacol. 130, 1369-1377.
66. Ozdemir M, Aktan Y, Boydag BS, Cingi MI & Musmul A (1998): Interaction between grapefruit juice and diazepam in humans. Eur. J. Drug Metab. Pharmacokinet. 23, 55-59.
67. Paine MF, Khalighi M, Fisher JM, Shen DD, Kunze KL, Marsh CL, Perkins JD & Thummel KE (1997): Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J. Pharmacol. Exp. Ther. 283, 1552-1562.
68. Phang JM, Poore CM, Lopaczynska J & Yeh GC (1993): Flavonol-stimulated efflux of 7,12-dimethylbenz(a)anthracene in multidrug-resistant breast cancer cells. Cancer Res. 53, 5977-5981.
69. Rashid J, McKinstry C, Renwick AG, Dirnhuber M, Waller DG & George CF (1993): Quercetin, an in vitro inhibitor of CYP3A, does not contribute to the interaction between nifedipine and grapefruit juice. Br. J. Clin. Pharmacol. 36, 460-463.
70. Rau SE, Bend JR, Arnold MO, Tran LT, Spence JD & Bailey DG (1997): Grapefruit juice-terfenadine single-dose interaction: magnitude, mechanism, and relevance. Clin. Pharmacol. Ther. 61, 401-409.
71. Rogers JD, Zhao J, Liu L, Amin RD, Gagliano KD, Porras AG, Blum RA, Wilson MF, Stepanavage M & Vega JM (1999): Grapefruit juice has minimal effects on plasma concentrations of lovastatin-derived 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Clin. Pharmacol. Ther. 66, 358-366.
72. Schmiedlin Ren P, Edwards DJ, Fitzsimmons ME, He K, Lown KS, Woster PM, Rahman A, Thummel KE, Fisher JM, Hollenberg PF & Watkins PB (1997): Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents. Decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins. Drug Metab. Dispos. 25, 1228-1233.
73. Sigusch H, Henschel L, Kraul H, Merkel U & Hoffmann A (1994): Lack of effect of grapefruit juice on diltiazem bioavailability in normal subjects. Pharmazie 49, 675-679.
74. Soldner A, Christians U, Susanto M, Wacher VJ, Silverman JA & Benet LZ (1999): Grapefruit juice activates P-glycoprotein-mediated drug transport. Pharm. Res. 16, 478-485.
75. Soons PA, Vogels BA, Roosemalen MC, Schoemaker HC, Uchida E, Edgar B, Lundahl J, Cohen AF & Breimer DD (1991): Grapefruit juice and cimetidine inhibit stereoselective metabolism of nitrendipine in humans. Clin. Pharmacol. Ther. 50, 394-403.
76. Spahn Langguth H & Langguth P (2001): Grapefruit juice enhances intestinal absorption of the P-glycoprotein substrate talinolol. Eur. J. Pharm. Sci. 12, 361-367.
77. Spence JD (1997): Drug interactions with grapefruit: whose responsibility is it to warn the public? Clin. Pharmacol. Ther. 61, 395-400.
78. Takanaga H, Ohnishi A, Matsuo H & Sawada Y (1998): Inhibition of vinblastine efflux mediated by P-glycoprotein by grapefruit juice components in caco-2 cells. Biol. Pharm. Bull. 21, 1062-1066.
79. Takanaga H, Ohnishi A, Murakami H, Matsuo H, Higuchi S, Urae A, Irie S, Furuie H, Matsukuma K, Kimura M, Kawano K, Orii Y. Tanaka T & Sawada Y (2000): Relationship between time after intake of grapefruit juice and the effect on pharmacokinetics and pharmacodynamics of nisoldipine in healthy subjects. Clin. Pharmacol. Ther. 67, 201-214.
80. Talajic M, DeRoode MR & Nattel S (1987): Comparative electrophysiologic effects of intravenous amiodarone and desethylamiodarone in dogs: evidence for clinically relevant activity of the metabolite. Circulation 75, 265-271.
81. Tian R, Koyabu N, Takanaga H, Matsuo H, Ohtani H & Sawada Y (2002): Effects of grapefruit juice and orange juice on the intestinal efflux of P-glycoprotein substrates. Pharm. Res. 19, 802-809.
82. Ubeaud G, Hagenbach J, Vandenschrieck S, Jung L & Koffel JC (1999): In vitro inhibition of simvastatin metabolism in rat and human liver by naringenin. Life Sci. 65, 1403-1412.
83. Uno T, Ohkubo T, Sugawara K, Higashiyama A, Motomura S & Ishizaki T (2000): 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. 56, 643-649.
84. Vanakoski J, Mattila MJ & Seppala T (1996): Grapefruit juice does not enhance the effects of midazolam and triazolam in man. Eur. J. Clin. Pharmacol. 50, 501-508.
85. Vincent J, Harris SI, Foulds G, Dogolo LC, Willavize S & Friedman HL (2000): Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine. Br. J. Clin. Pharmacol. 50, 455-463.
86. Wang EJ, Casciano CN, Clement RP & Johnson WW (2001): Inhibition of P-glycoprotein transport function by grapefruit juice psoralen. Pharm. Res. 18, 432-438.
87. Williams D & Feely J (2002): Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clin. Pharmacokinet. 41, 343-370.
88. Woosley RL, Chen Y, Freiman JP & Gillis RA (1993): Mechanism of the cardiotoxic actions of terfenadine. JAMA 269, 1532-1536.
89. Yasui N, Kondo T, Furukori H, Kaneko S, Ohkubo T, Uno T, Osanai T, Sugawara K & Otani K (2000): Effects of repeated ingestion of grapefruit juice on the single and multiple oral-dose pharmacokinetics and pharmacodynamics of alprazolam. Psychopharmacology (Berl) 150, 185-190.
90. Yee GC, Stanley DL, Pessa LJ, Dalla Costa T, Beltz SE, Ruiz J & Lowenthal DT (1995): Effect of grapefruit juice on blood cyclosporin concentration. Lancet 345, 955-956.
91. Yun CH, Okerholm RA & Guengerich FP (1993): Oxidation of the antihistaminic drug terfenadine in human liver microsomes. Role of cytochrome P-450 3A(4) in N-dealkylation and C-hydroxylation. Drug Metab. Dispos. 21, 403-409.
92. Zaidenstein R, Dishi V, Gips M, Soback S, Cohen N, Weissgarten J, Blatt A & Golik A (1998): The effect of grapefruit juice on the pharmacokinetics of orally administered verapamil. Eur. J. Clin. Pharmacol. 54, 337-340.
93. Zhang QY, Dunbar D, Ostrowska A, Zeisloft S, Yang J & Kaminsky LS (1999): Characterization of human small intestinal cytochromes P-450. Drug Metab. Dispos. 27, 804-809.
94. Zhou L, Chen BP, Kluger J, Fan C & Chow MS (1998): Effects of amiodarone and its active metabolite desethylamiodarone on the ventricular defibrillation threshold. J. Am. Coll. Cardiol. 31, 1672-1678.