Inhibition of Terfenadine Metabolism in Vitro by Azole Antifungal Agents and by Selective Serotonin Reuptake Inhibitor Antidepressants: Relation to Pharmacokinetic Interactions in Vivo

Journal of Clinical Psychopharmacology

Volumn 16, Issue 2, 1996, Pages 104-112

  Von Moltke, Lisa L ^a,b   Greenblatt, David J ^a,b   Xiang Duan, S U ^a,b   Harmatz, Jerold S ^a,b   Eugene Wright, C ^c   Shader, Richard I ^a,b  

^a TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b TUFTS MEDICAL CENTER   (United States)

^c PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIDEPRESSANT AGENT; ANTIFUNGAL AGENT; CYTOCHROME P450; FLUCONAZOLE; FLUOXETINE; FLUVOXAMINE; ITRACONAZOLE; KETOCONAZOLE; NORFLUOXETINE; NORSERTRALINE; PAROXETINE; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; TERFENADINE;

ARTICLE; BIOTRANSFORMATION; DRUG ANTAGONISM; DRUG METABOLISM; HUMAN; HUMAN TISSUE; IN VITRO STUDY; LIVER; PRIORITY JOURNAL;

ANTIFUNGAL AGENTS; ARYL HYDROCARBON HYDROXYLASES; BIOTRANSFORMATION; CULTURE TECHNIQUES; CYTOCHROME P-450 CYP3A; CYTOCHROME P-450 ENZYME SYSTEM; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG INTERACTIONS; HISTAMINE H1 ANTAGONISTS; HUMANS; KETOCONAZOLE; METABOLIC CLEARANCE RATE; MICROSOMES, LIVER; OXIDOREDUCTASES, N-DEMETHYLATING; SEROTONIN UPTAKE INHIBITORS; TERFENADINE;

EID: 0030009690     PISSN: 02710749     EISSN: None     Source Type: Journal    
DOI: 10.1097/00004714-199604000-00002     Document Type: Article

References (77)

1. Sorkin EM, Heel RC. Terfenadine: a review of its pharmacodynamic properties and therapeutic efficacy. Drugs 1985;29:34-56.
2. Garteiz DA, Hook RH, Walker BJ, Okerholm RA. Pharmacokinetics and biotransformation studies of terfenadine in man. Arzneimittelforschung 1982;32:1185-90.
3. Jurima-Romet M, Crawford K, Cyr T, Inaba T. Terfenadine metabolism in human liver: in vitro inhibition by macrolide antibiotics and azole antifungals. Drug Metab Dispos 1994;22:849-57.
4. Yun C-H, Okerholm RA, Guengerich FP. 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 1993;21:403-9.
5. von Moltke LL, Greenblatt DJ, Duan SX, Harmatz JS, Shader RI. In vitro prediction of the terfenadine-ketoconazole pharmacokinetic interaction. J Clin Pharmacol 1994;34:1222-7.
6. Ling K-HJ, Leeson GA, Burmaster SD, Hook RH, Reith MK, Cheng LK. Metabolism of terfenadine associated with CYP3A(4) activity in human hepatic microsomes. Drug Metab Dispos 1995;23:631-6.
7. Rodrigues AD, Mulford DJ, Lee RD, Surber BW, Kukulka MJ, Ferrero JL, Thomas SB, Shet MS, Estabrook RW. In vitro metabolism of terfenadine by a purified recombinant fusion protein containing cytochrome P4503A4 and NADPH-P450 reductase. Drug Metab Dispos 1995;23:765-75.
8. Newton DJ, Wang RW, Lu AYH. Cytochrome P450 inhibitors, evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab Dispos 1995;23:154-8.
9. Gascon M-P, Dayer P. In vitro forecasting of drugs which may interfere with the biotransformation of midazolam. Eur J Clin Pharmacol 1991;41:573-8.
10. von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, Harmatz JS, Shader RI. Inhibitors of alprazolam metabolism in vitro: effect of serotonin-reuptake-inhibitor antidepressants, ketoconazole and quinidine. Br J Clin Pharmacol 1994;38:23-31.
11. Swinney DC. Progesterone metabolism in hepatic microsomes. Drug Metab Dispos 1990;18:859-65.
12. Back DJ, Tjia JF. Comparative effects of the antimycotic drugs ketoconazole, fluconazole, itraconazole and terbinafine on the metabolism of cyclosporin by human liver microsomes. Br J Clin Pharmacol 1991;32:624-6.
13. Maurice M, Pichard L, Daujat M, Fabre I, Joyeux H, Domergue J, Maurel P. Effects of imidazole derivatives on cytochromes P450 from human hepatocytes in primary culture. FASEB J 1992;6:752-8.
14. Honig PK, Wortham DC, Zamani K, Conner DP, Mullin JC, Cantilena LR. Terfenadine-ketoconazole interaction: pharmacokinetic and electrocardiographic consequences. JAMA 1993;269:1513-8.
15. Honig PK, Wortham DC, Hull R, Zamani K, Smith JE, Cantilena LR. Itraconazole affects single-dose terfenadine pharmacokinetics and cardiac repolarization pharmacodynamics. J Clin Pharmacol 1993;33:1201-6.
16. Honig PK, Wortham DC, Zamani K, Mullin JC, Conner DP, Cantilena LR, The effect of fluconazole on the steady-state pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine in humans. Clin Pharmacol Ther 1993;53:630-6.
17. Monahan BP, Ferguson CL, Killeavy ES, Lloyd BK, Troy J, Cantilena LR. Torsades de pointes occurring in association with terfenadine use. JAMA 1990;264:2788-90.
18. Woosley RL, Chen Y, Freiman JP, Gillis RA. Mechanism of the cardiotoxic actions of terfenadine. JAMA 1993;269:1532-6.
19. + channel cloned from human heart. Mol Pharmacol 1993;44:1240-5.
20. Crumb WJ, Wible B, Arnold DJ, Payne JP, Brown AM. Blockade of multiple human cardiac potassium currents by the antihistamine terfenadine: possible mechanism for terfenadine-associated cardiotoxicity. Mol Pharmacol 1995;47:181-90.
21. van Harten J. Clinical pharmacokinetics of selective serotonin reuptake inhibitors. Clin Pharmacokinet 1993;24:203-20.
22. Rasmussen BB, Mäenpää J, Pelkonen O, Loft S, Poulsen HE, Lykkesfeldt J, Brswslosen K. Selective serotonin reuptake inhibitors and theophylline metabolism in human liver microsomes: potent inhibition by fluvoxamine. Br J Clin Pharmacol 1995;39:151-9.
23. von Moltke LL, Greenblatt DJ, Court MH, Duan SX, Harmatz JS, Shader RI. Inhibition of alprazolam and desipramine hydroxylation in vitro by paroxetine and fluvoxamine: comparison with other selective serotonin reuptake inhibitor antidepressants. J Clin Psychopharmacol 1995;15:125-31.
24. von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, Duan SX, Harmatz JS, Shader RI. Inhibition of desipramine hydroxylation in vitro by serotonin-reuptake-inhibitor antidepressants, and by quinidine and ketoconazole: a model system to predict drug interactions in vivo. J Pharmacol Exp Ther 1994;268:1278-83.
25. von Moltke LL, Greenblatt DJ, Harmatz JS, Shader RL Alprazolam metabolism in vitro: studies of human, monkey, mouse, and rat liver microsomes. Pharmacology 1993;47:268-76.
26. Coutant JE, Westmark PA, Nardella PA, Walter SM, Okerholm RA. Determination of terfenadine and terfenadine acid metabolite in plasma using solid-phase extraction and high-performance liquid chromatography with fluorescence detection. J Chromatography 1991;570:139-48.
27. Chen TM, Chan KY, Coutant JE, Okerholm RA. Determination of the metabolites of terfenadine in human urine by thermospray liquid chromatography-mass spectrometry. J Pharmaceut Biomed Anal 1991;9:929-33.
28. Andersson T, Miners JO, Veronese ME, Birkett DJ. Diazepam metabolism by human liver microsomes is mediated by both S-mephehytoin hydroxylase and CYP3A isoforms. Br J Clin Pharmacol 1994;38:131-7.
29. Schmider J, Greenblatt DJ, von Moltke LL, Harmatz JS, Shader RI. N-demethylation of amitriptyline in vitro, role of Cytochrome P-450 3A (CYP3A) isoforms, and effect of metabolic inhibitors. J Pharmacol Exp Ther 1995;275:592-7.
30. Shou M, Grogan J, Mancewicz JA, Krausz KW, Gonzalez FJ, Gelboin HV, Korzekwa KR. Activation of CYP3A4: evidence for the si- multaneous binding of two substrates in a cytochrome P450 active site. Biochemistry 1994;33:6450-5.
31. Schwab GE, Raucy JL, Johnson EF. Modulation of rabbit and human hepatic cytochrome P-450-catalyzed steroid hydroxylations by α-naphthoflavone. Mol Pharmacol 1988;33:493-9.
32. i for conventional and alternate-substrate inhibitors. Biochem Pharmacol 1981;30:1-7.
33. Tucker GT. The rational selection of drug interaction studies: implications of recent advances in drug metabolism. Int J Clin Pharmacol Ther Toxicol 1992;30:550-3.
34. von Moltke LL, Greenblatt DJ, Schmider J, Harmatz JS, Shader RI. Metabolism of drugs by Cytochrome P450-3A isoforms: implications for drug interactions in psychopharmacology. Clin Pharmacokinet 1995;29[suppl 1]:33-43.
35. Bergstrom RF, Wolen RL, Lemberger L, Tenbarge JL, Masco HL. Fluoxetine steady-state pharmacokinetics in depressed patients. Presented at the 133rd Annual Meeting of the American Pharmaceutical Association, San Francisco CA, March 1986:16-20.
36. Preskorn SH, Alderman J, Chung M, Harrison W, Messig M, Harris S. Pharmacokinetics of desipramine coadministered with sertraline or fluoxetine. J Clin Psychopharmacol 1994;14:90-8.
37. Kaye CM, Haddock RE, Langley PF, Mellows G, Tasker TCG, Zussman BD, Greb WH. A review of the metabolism and pharmacokinetics of paroxetine in man. Acta Psychiatr Scand 1989;80[suppl 350]:60-75.
38. LUVOX (Fluvoxamine maleate) product labeling. Solvay Pharmaceuticals, Marietta, GA, 1994.
39. Chou C-H, Evans AM, Fornasini G, Rowland M. Relationship between lipophilicity and hepatic dispersion and distribution for a homologous series of barbiturates in the isolated perfused in situ rat liver. Drug Metab Dispos 1993;21:933-8.
40. Fraser AD, Isner AF, Perry RA. Distribution of trimipramine and its major metabolites in a fatal overdose case. J Anal Toxicol 1987;11:168-70.
41. Wong RJ. The determination of the triazolobenzodiazepine triazolam in post mortem samples. J Anal Toxicol 1984;8:10-3.
42. Igari Y, Sugiyama Y, Sawada Y, Iga T, Hanano M. Prediction of diazepam disposition in the rat and man by a physiologically based pharmacokinetic model. J Pharmacokinet Biopharm 1983;11:577-93.
43. Scavone JM, Friedman H, Greenblatt DJ, Shader RI. Effect of age, body composition, and lipid solubility on benzodiazepine tissue distribution in rats. Arzneimittelforschung 1987;37:2-6.
44. Bailey DN, Shaw RF. Interpretation of blood and tissue concentrations in fatal self-ingested overdose involving amitriptyline: an update (1978-1979). J Anal Toxicol 1980;4:232-6.
45. Levine B, Jenkins AJ, Smialek JE. Distribution of sertraline in postmortem cases. J Anal Toxicol 1994;18:272-4.
46. von Moltke LL, Greenblatt DJ, Harmatz JS, Duan SX, Harrel LM, Cotreau-Bibbo MM, Pritchard GA, Wright CE, Shader RI. Triazolam biotransformation by human liver microsomes in vitro: effects of metabolic inhibitors, and clinical confirmation of a predicted interaction with ketoconazole. J Pharmacol Exp Ther 1996;276:370-9.
47. Riley CM, James MO. Determination of ketoconazole in the plasma, liver, lung and adrenal of the rat by high-performance liquid chromatography. J Chromatogr 1986;377:287-94.
48. Matthew D, Brennan B, Zomorodi K, Houston JB. Disposition of azole antifungal agents. I. Nonlinearities in ketoconazole clearance and binding in rat liver. Pharmaceut Res 1993;10:418-22.
49. Heykants J, van Peer A, van de Velde V, van Rooy P, Meuldermans W, Lavrijsen K, Woestenborghs R, van Cutsem J, Cauwenbergh G. The clinical pharmacokinetics of itraconazole: an overview. Mycoses 1989;32[suppl 1]:67-87.
50. Heykants J, Michiels M, Meuldermans W, Monbaliu J, Lavrijsen K, van Peer A, Levron JC, Woestenborghs R, Cauwenbergh G. The pharmacokinetics of itraconazole in animal and man: an overview. In: Fromtling RA, ed. Recent trends in the discovery, development and evaluation of antifungal agents. Barcelona, Spain: JR Prous Science Publishers, 1987:223-49.
51. Kolars JC, Lown KS, Schmiedlin-Ren P, Ghosh M, Fang C, Wrighton SA, Merion RM, Watkins PB. CYP3A gene expression in human gut epithelium. Pharmacogenetics 1994;4:247-59.
52. Kolars JG, Schmiedlin-Ren P, Schuetz JD, Fang C, Watkins PB, Identification of rifampin-inducible, P450IIIA4 (CYP3A4) in human small bowel enterocytes. J Clin Invest 1992;90:1871-8.
53. Gomez DY, Wacher VJ, Tomlanovich SJ, Hebert MF, Benet LZ. The effects of ketoconazole on the intestinal metabolism and bioavailability of cyclosporine. Clin Pharmacol Ther 1995;58:15-9.
54. Kuang TY, Morgan A, Lazarev A, Cantilena LR. Human CYP3A4 as a potential in vitro screening system for terfenadine drug interactions [abstract]. Clin Pharmacol Ther 1994;55:139.
55. Kuang TY, Cantilena LR. Terfenadine-ketoconazole metabolite interaction in human liver microsomes of male and female subjects [abstract]. Clin Pharmacol Ther 1995;57:185.
56. 9 fractions [abstract]. Clin Pharmacol Ther 1995;57:185.
57. Cantilena LR, Sorrels S, Wiley T, Wortham D. Fluconazole alters terfenadine pharmacokinetics and electrocardiographic pharmacodynamics [abstract]. Clin Pharmacol Ther 1995;57:185.
58. Kivistö KT, Neuvonen PJ, Klotz U. Inhibition of terfenadine metabolism: pharmacokinetic and pharmacodynamic consequences. Clin Pharmacokinet 1994;27:1-5.
59. Honig PK, Wortham DC, Zamani K, Cantilena LR. Comparison of the effect of the macrolide antibiotics erythromycin, clarithromycin and azithromycin on terfenadine steady-state pharmacokinetics and electrocardiographic parameters. Drug Invest 1994;7:148-56.
60. Roos PH, Golub-Ciosk B, Kallweit P, Kauczinski D, Hanstein WG. Formation of ligand and metabolite complexes as a means for selective quantitation of cytochrome P450 isozymes. Biochem Pharmacol 1993;45:2239-50.
61. Echizen H, Kawasaki H, Chiba K, Tard M, Ishizaki T. A potent inhibitory effect of erythromycin and other macrolide antibiotics on the mono-N-dealkylation metabolism of disopyramide with human liver microsomes. J Pharmacol Exp Ther 1993;264:1425-31.
62. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF. The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clin Pharmacol Ther 1988;43:412-9.
63. Lasher TA, Fleishaker JC, Steenwyk RC, Antal EJ. Pharmacokinetic pharmacodynamic evaluation of the combined administration of alprazolam and fluoxetine. Psychopharmacology 1991;104:323-7.
64. Greenblatt DJ, Preskorn SH, Cotreau MM, Horst WD, Harmatz JS. Fluoxetine impairs clearance of alprazolam but not of clonazepam. Clin Pharmacol Ther 1992;52:479-86.
65. Fleishaker JC, Hulst LK. A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine. Eur J Clin Pharmacol 1994;46:35-9.
66. Perucca E, Gatti G, Cipolla G, Spina E, Barel S, Sobaek S, Gips M, Bialer M. Inhibition of diazepam metabolism by fluvoxamine: a pharmacokinetie study in normal volunteers. Clin Pharmacol Ther 1994;56:471-6.
67. El-Yazigi A, Chaleby K, Gad A, Raines DA. Steady-state kinetics of fluoxetine and amitriptyline in patients treated with a combination of these drugs as compared with those treated with amitriptyline alone. J Clin Pharmacol 1995;35:17-21.
68. von Moltke LL, Greenblatt DJ, Schmider J, Harmatz JS, Shader RI. Nefazodone in vitro: metabolic conversions, and inhibition of P450-3A isoforms [abstract]. Clin Pharmacol Ther 1996;59:176.
69. Kroboth PD, Folan MM, Lush RM, Chaikin PC, Shukla UA, Barbhaiya RH, Salazar DE. Coadministration of nefazodone and benzodiazepines: I. pharmacodynamic assessment J Clin Psychopharmacol 1995;15:306-19.
70. Barbhaiya RH, Shukla UA, Kroboth PD, Greene DS. Coadministration of nefazodone and benzodiazepines: II. a pharmacokinetic interaction study with triazolam. J Clin Psychopharmacol 1995;15:320-6.
71. Greene DS, Salazar DE, Dockens RC, Kroboth P, Barbhaiya RH, Coadministration of nefazodone and benzodiazepines: III. Pharmacokinetic interaction study with alprazolam. J Clin Psychopharmacol 1995;15:399-408.
72. Swims MP. Potential terfenadine-fluoxetine interaction. Ann Pharmacother 1993;27:1404-5.
73. Marchaindo RJ, Cook MD, Jue SG. Possible terfenadine-fluoxetine-associated cardiac toxicity. Ann Pharmacother 1995;29:937-8.
74. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 1994;270:414-23.
75. Stoll AL, Pope HG, McElroy SL. High-dose fluoxetine: safety and efficacy in 27 cases. J Clin Psychopharmacol 1991;11:225-6.
76. Oberg KC, Bauman JL. QT prolongation and Torsades des Pointes due to erythromycin lactobionate. Pharmacotherapy 1995;15:687-92.
77. Pascheria LA, Hewett J, Woosley RL. Effects of ketoconazole on QTC [abstract]. Clin Pharmacol Ther 1994;55:146.