Flavin-containing monooxygenase-mediated metabolism of N-deacetyl ketoconazole by rat hepatic microsomes

Drug Metabolism and Disposition

Volumn 27, Issue 8, 1999, Pages 880-886

  Rodriguez, Rosita J ^a   Proteau, Philip J ^a   Marquez, Brian L ^a   Hetherington, Craig L ^a   Buckholz, Cheryl J ^a   O'Connell, Kerry L ^a  

^a OREGON STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FLAVOPROTEIN; KETOCONAZOLE; UNSPECIFIC MONOOXYGENASE;

ANIMAL EXPERIMENT; ARTICLE; DEACETYLATION; DRUG OXIDATION; ENZYME ACTIVITY; FEMALE; LIVER MICROSOME METABOLISM; LIVER TOXICITY; MALE; NONHUMAN; PRIORITY JOURNAL; RAT; TOXICITY TESTING;

ANIMALS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; FEMALE; FLAVINS; KETOCONAZOLE; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MASS SPECTROMETRY; MICE; MICROSOMES, LIVER; MIXED FUNCTION OXYGENASES; OXIDATION-REDUCTION; PIPERAZINES; RATS; RATS, SPRAGUE-DAWLEY;

EID: 0032807193     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (39)

1. Achari R and Beckett AH (1983) In-vitro metabolism of two mono-substituted piperazines using liver homogenates of rats and rabbits. J Pharm Pharmacol 35:615-616.
2. Benson GD, Anderson PK, Combes B and Ishak KG (1988) Prolonged jaundice following ketoconazole-induced hepatic injury. Dig Dis Sci 33:240-246.
3. Bercoff E, Bernuau J, Degott C, Kalis B, Lamaire A, Tilly H, Rueff B and Benhamou JP (1985) Ketoconazole-induced fulminant hepatitis. Gut 26:636-638.
4. Biloski AJ and Ganem B (1983) Improved oxidation of amines with dibenzoyl peroxide. Synthesis 537-538.
5. Bodey GP (1992) Azole antifungal agents. Clin Infect Dis 14(Suppl):S161-S169.
6. Brusko CS and Marten JT (1991) Ketoconazole hepatotoxicity in a patient treated for environmental illness and systemic candidiasis. Ann Pharmacother 25:1321-1325.
7. Cashman JR and Ziegler DM (1986) Contribution of N-oxygenation to the metabolism of MPTP (1-methyl-4-phenyl-1.2,3,6-tetrahyropyridine) by various liver preparations. Mol Pharmacol 29:163-167.
8. Cherrington NJ, Cao Y, Cherrington JW, Rose RL and Hodgson E (1998) Physiological factors affecting protein expression of flavin-containing monooxygenases 1, 3, and 5. Xenobiotica 28:673-682.
9. Daneshmend TK and Warnock DW (1988) Clinical pharmacokinetics of ketoconazole. Clin Pharmacokinet 14:13-34.
10. Dannan GA, Guengerich FP and Waxman DJ (1986) Hormonal regulation of rat liver microsomal enzymes. J Biol Chem 261:10728-10735.
11. Gascoigne EW, Barton GJ, Michaels M, Meuldermans W and Heykants J (1981) The kinetics of ketoconazole in animals and man. Clin Res Rev 1:177-187.
12. Hann SK, Kim JB, Im S, Man KH and Park YK (1993) Itraconazole-induced acute hepatitis. Br J Dermatol 129:500-501.
13. Heel RC, Brogden RN, Carmine A, Morley PA, Speight TM and Avery GS (1982) Ketoconazole: A review of its therapeutic efficacy in superficial and systemic fungal infections. Drugs 23:1-36.
14. Ho Y-S, Tsai P-W, Yu C-F, Liu H-L, Chen R-J and Lin J-K (1998) Ketoconazole-induced apoptosis through P53-dependent pathway in human colorectal and hepatocellular carcinoma cell lines. Toxicol Appl Pharmacol 153:39-47.
15. Jacobson MA, Hanks DK and Ferrell LD (1994) Fatal acute hepatic necrosis due to fluconazole. Am J Med 96:188-190.
16. Janssen PA and Symoens JE (1983) Hepatic reactions during ketoconazole treatment. Am J Med 74:80-85.
17. Jubelirer SJ and Hogan T (1989) High dose ketoconazole for the treatment of hormone refractory metastatic prostate carcinoma: 16 cases and review of the literature. J Urol 142:89-91.
18. Kadlubar FF, McKee EM and Ziegler DM (1973) Reduced pyridine nucleotide-dependent N-hydroxy amine oxidase and reductase activities of hepatic microsomes. Arch Biochem Biophys 156:46-57.
19. Knight TE, Shikuma CY and Knight J (1991) Ketoconazole-induced fulminant hepatitis necessitating liver transplantation. J Am Acad Dermatol 25:398-400.
20. Lavrijsen APM, Balmus KJ, Nugtern-Huying WM, Robdaan AC, van't Wout, JW and Stricker BHC (1992) Hepatic injury associated with itraconazole. Lancet 340:251-252.
21. Lemoine A, Williams DE, Cresteil T and Leroux JP (1991) Hormonal regulation of microsomal flavin-containing monooxygenase: Tissue-dependent expression and substrate specificity. Mol Pharmacol 40:211-217.
22. Maurice M, Pichard L, Daujat M, Fabre I, Joyeux H, Domergue J and Maurel P (1992) Effects of imidazole derivatives on cytochrome P450 from human hepatocytes in primary culture. FASEB J 6:752-758.
23. Miranda CL, Chung W, Reed RE, Zhao X, Henderson MC, Wang JL, Williams DE and Buhler DR (1991) Flavin-containing monooxygenase: A major detoxifying enzyme for the pyrrolizidine alkaloid senecionine in guinea pig tissues. Biochem Biophys Res Commun 178:546-552.
24. Pont A, Graybill JR, Craven PC, Galgiani JN, Dismukes WE, Reitz RE and Stevens DA (1984) High-dose ketoconazole therapy and adrenal and testicular function in humans. Arch Intern Med 144:2150-2153.
25. Ringel SM (1990) New antifungal agents for the systemic mycoses. Mycopathologia 109:77-87.
26. Rodriguez RJ and Acosta D (1997a) Metabolism of ketoconazole and deacetylated ketoconazole by rat hepatic microsomes and flavin-containing monooxygenases. Drug Metab Dispos 25:772-777.
27. Rodriguez RJ and Acosta D (1997b) N-deacetyl ketoconazole-induced hepatotoxicity in a primary culture system of rat hepatocytes. Toxicology 117:123-131.
28. Skett P, Mode A, Rafter J, Sahlin L and Gustafsson J-A (1980) The effects of gonadectomy and hypophysectomy on the metabolism of imipramine and lidocaine by the liver of male and female rats. Biochem Pharmacol 29:2759-2762.
29. Strandberg TE, Tilvis RS and Miettinen TA (1987) Effects of ketoconazole on cholesterol synthesis and precursor concentrations in the rat liver. Lipids 22:1020-1024.
30. Stricker BHC, Blok APR, Bronkhorst FB, Van Parys GE and Desmet VJ (1986) Ketoconazole-associated hepatic injury a clinicopathological study of 55 cases. J Hepatol 3:399-406.
31. Van Den Bossche H, Willemsens G, Cools W, Comelissen F, Lauwers WF and Van Cutsen JM (1980) In vitro and in vivo effects of the antimycotic drug ketoconazole on sterol synthesis. Antimicrob Agents Chemother 17:922-928.
32. Van Parys G, Evenepoel C, Van Damme B and Desmet VJ (1987) Ketoconazole-induced hepatitis: A case with a definite cause-effect relationship. Liver 7:27-30.
33. Vogelzang NJ and Kennealey GT (1992) Recent development in endocrine treatment of prostate cancer. Cancer 70:966-975.
34. Wells C and Lever AML (1992) Dose dependent fluconazole hepatotoxicity proven on biopsy and rechallenge. J Infect 24:111-112.
35. Whitehouse LW, Menzies A, Dawson B, Cyr TD, By AW, Black DB and Zamecnik J (1994a) Mouse hepatic metabolites of ketoconazole: Isolation and structure elucidation. J Pharm Biomed Anal 12:1425-1441.
36. Whitehouse LW, Menzies A, Dawson B, Zamecnik J and Sy WW (1990) Deacetylated ketoconazole: a major ketoconazole metabolite isolated from mouse liver. J Pharm Biomed Anal 8:603-606.
37. Whitehouse LW, Menzies A, Mueller R and Pontefract R (1994b) Ketoconazole-induced hepatic phospholipidosis in the mouse and its association with de-N-acetyl ketoconazole. Toxicology 94:81-95.
38. Ziegler DM (1980) Microsomal flavin-containing monooxygenase: Oxygenation of nucleophilic nitrogen and sulfur compounds, in Enzymatic Basis of Detoxication, vol 1, pp 201-227, Academic Press, New York.
39. Ziegler DM (1988) Flavin-containing monooxygenases: Catalytic mechanism and substrate specificities. Drug Metabol Rev 19:1-32.