The metabolic profile of azimilide in man: In vivo and in vitro evaluations

Journal of Pharmaceutical Sciences

Volumn 94, Issue 9, 2005, Pages 2084-2095

  Riley, P ^a   Figary, P C ^a   Entwisle, J R ^a   Roe, A L ^a   Thompson, G A ^a   Ohashi, R ^b   Ohashi, N ^b   Moorehead, T J ^a  

^a PROCTER AND GAMBLE PHARMACEUTICALS   (United States)

^b Exploratory Toxicology and Drug Metabolism and Pharmacokinetics   (Japan)

Author keywords

Cytochrome P450; Drug metabolizing enzymes; Flavin monooxygenases; Mass balance; Metabolism; Monoamine oxidase; Xanthine oxidase

Indexed keywords

4 CHLORO 2 PHENYLFUROIC ACID; AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME B; AZIMILIDE; AZIMILIDE N OXIDE; BUTYRIC ACID DERIVATIVE; CARBON 14; CYTOCHROME B5; CYTOCHROME P450 1A1; CYTOCHROME P450 1A2; CYTOCHROME P450 2A6; CYTOCHROME P450 2B6; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 3A4; CYTOCHROME P450 4A; DRUG METABOLITE; FLAVIN MONOOXYGENASE; HYDANTOIN DERIVATIVE; MYELOPEROXIDASE; NORAZIMILIDE; PHENOL DERIVATIVE; UNCLASSIFIED DRUG; UNSPECIFIC MONOOXYGENASE; XANTHINE OXIDASE;

ADULT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DEMETHYLATION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DEGRADATION; DRUG FECES LEVEL; DRUG METABOLISM; DRUG OXIDATION; DRUG URINE LEVEL; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; IN VITRO STUDY; IN VIVO STUDY; LIVER MICROSOME; MALE; MASS SPECTROMETRY; NORMAL HUMAN; RADIOMETRY;

EID: 27644498400     PISSN: 00223549     EISSN: None     Source Type: Journal    
DOI: 10.1002/jps.20429     Document Type: Article

References (28)

1. Karam R, Marcello S, Brooks RR, Corey AE, Moore A. 1998. Azimilide dihydrochloride, a novel antiarrhythmic agent. Am J Cardiol 81:40D-46D.
2. Al-Khalidi HR, Brum J, Hislop C, Gunderson L, Singer I, Sager P. 2000. Azimilide reduces the frequency of shocks in patients with an implantable cardioverter defibrillator programmed for pacing and shock: Andersen-Gill Model. PACE 23:566.
3. Salata JJ, Brooks RR. 1997. Pharmacology of azimilide hydrochloride (NE-10064), a class III antiarrhythmic agent. Cardiovasc Drugs Rev 15:137-156.
4. Dorian P, Dunnmon P, Elstun L, Newman D. 2002. The effect of isoproterenol on the class III effect of azimilide in humans. J Cardiovasc Pharmacol Ther 7:211-217.
5. Camm AJ, Pratt C, Schwartz PJ, Al-Khalidi HR, Spyt M, Holroyd MJ, Karam R, Sonnenblick EH, Brum JM. 2001. Azimilide post-infarct survival evaluation (ALIVE): Azimilide does not affect mortality in post-myocardial infarction patients. Circulation 104:1B.
6. Connolly SJ, Schnell DJ, Page RL, Wilkinson WE, Marcello SR, Pritchett ELC. 2001. Dose-response relations of azimilide in the management of symptomatic, recurrent, atrial fibrillation. Am J Cardiol 88:974-979.
7. Gibson GG, Skett P. 1994. Introduction to drug metabolism. 2nd edn. London: Blackie Academic & Professional.
8. Tassaneeyakul W, Birkett DJ, Veronese ME, McManus ME, Tukey RH, Quattrochi LC, Gelboin HV, Miners JO. 1993. Specificity of substrate and inhibitor probes for human cytochromes P4501A1 and 1A2. J Pharmacol Exp Ther 265:401-407.
9. Greenlee WF, Poland A. 1978. An improved assay of 7-ethoxycoumarin O-deethylase activity: Induction of hepatic enzyme activity in C57BL/6J and DBA/2J mice by phenobarbital, 3-methylcholanthrene and 2,3,7,8- tetrachlorodibenzo-p-dioxin. J Pharm Exp Ther 205:596-605.
10. Heyn H, White RB, Stevens JC. 1996. Catalytic role of cytochrome P4502B6 in the N-demethylation of S-mephenytoin. Drug Metab Dispos 24:948-954.
11. Yasar U, Eliasson E, Forslund-Bergengren C, Tybring G, Gadd M, Sjoqvist F, Dahl ML. 2001. The role of CYP2C9 genotype in the metabolism of diclofenac in vivo and in vitro. Eur J Clin Pharmacol 57:729-735.
12. Wrighton SA, Stevens JC, Becker GW, Vanden Branden M. 1993. Isolation and characterization of human liver cytochrome P4502C19: Correlation between 2C19 and S-mephenytoin 4′-hydroxylation. Arch Biochem Biophys 306:240-245.
13. Kronbach T, Mathys D, Gut J, Catin T, Meyer UA. 1987. High-performance liquid chromatographic assays for bufuralol 1′-hydroxylase, debrisoquine 4-hydroxylase, and dextromethorphan O-demethylase in microsomes and purified cytochrome P-450 isozymes of human liver. Anal Biochem 162:24-32.
14. Buters JTM, Korzekwa KR, Kunze KL, Omata Y, Hardwick JP, Gonzales FJ. 1994. cDNA-directed expression of human cytochrome P450 CYP3A4 using baculovirus. Drug Metab Disp 22:688-692: 1001-1007.
15. Omura T, Sato R. 1964. The carbon monoxide-binding pigment of liver microsomes I. Evidence for its hemoprotein nature. J Biol Chem 239:2370-2378.
16. Brunelle A, Bi YA, Lin J, Russell B, Luy L, Berkman C, Cashman J. 1997. Characterization of two human flavin-containing monooxygenase (form 3) enzymes expressed in Escherichia coli as maltose binding protein fusions. Drug Metab Dispos 25:1001-1007.
17. Cashman J. 1997. Monoamine oxidase and flavin-containing monooxygenases. In: Sipes IG, McQueen CA, Gandolfi AJ, editors. Comprehensive Toxicology. Vol. 3. New York: Elsevier Science, pp 69-96.
18. Fuchs P, Haefeli WE, Ledermann HR, Wenk M. 1999. Xanthine oxidase inhibition by allopurinol affects the reliability of urinary caffeine metabolic ratios as markers for N-acetyltransferase 2 and CYP1A2 activities. Eur J Clin Pharmacol 54:869-876.
19. Eagling VA, Tjia JF, Back DJ. 1998. Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes. Br Clin Pharmacol 45:107-114.
20. Bourrie M, Meunier V, Berger Y, Fabre G. 1996. Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes. J Pharmacol Exp Ther 277:321-332.
21. Yamazaki H, Shimada T. 1998. Comparative studies of in vitro inhibition of cytochrome P4503A4-dependent testosterone 6 beta-hydroxylation by roxithromycin and its metabolites, troleandomycin and erythromycin. Drug Metab Dispos 26:1053-1057.
22. Thompson GA, Burgio DE. 2004. The role of metabolite pharmacokinetics and pharmacodynamics in drug development. In: Bonate PL, Howard DR, editors. Pharmacokinetics in Drug Development Volume 1: Clinical Study Design and Analysis. Arlington, VA: AAPS Press. pp 321-346.
23. Corey AE, Agnew JR, Valentine SN, Parekh NJ, Powell JH, Thompson GA. 2002. Effect of severe renal impairment on the pharmacokinetics of azimilide following single dose oral administration. Br J Clin Pharmacol 54:449-452.
24. Corey AE, Agnew JR, King EC, Parekh NJ, Powell JH, Thompson GA. 2004. Effect of mild and moderate hepatic impairment on azimilide pharmacokinetics following single dose oral administration. J Pharm Sci 93:1279-1286.
25. Bailey MJ, Dickinson RG. 2003. Acyl glucuronide reactivity in perspective: Biological consequences. Chemico-Biol Interact 145:117.
26. Ramu K, Lam GN, Hughes H. 2000. In vivo metabolism and mass balance of 4-[4-fluorophenoxy]benzaldehyde semicarbazone in rats. Drug Metab Dispos 28:1153-1161.
27. Phillips L, Grasela TH, Agnew JR, Ludwig EA, Thompson GA. 2001. A population pharmacokinetic-pharmacodynamic analysis and model validation of azimilide. Clin Pharmacol Ther 70:370-383.
28. El Mouelhi M, Worley DJ, Kuzmak B, Destefano AJ, Thompson GA. 2004. Influence of azimilide on CYP2C19-mediated metabolism. J Clin Pharmacol 44:373-378.