title: Climbazole is a new potent inducer of rat hepatic cytochrome P450.
abstract: We examined the effect of climbazole on the induction of rat hepatic microsomal cytochrome P450 (P450), and compared the induction potency with other N-substituted azole drugs such as clorimazole. We found that climbazole is found to be a potent inducer of rat hepatic microsomal P450 as clorimazole. Induced level of P450 by climbazole was almost similar in extent to clorimazole when compared with other imidazole drugs in a dose- and time-dependent manner. Parallel to the increase in P450, climbazole increased aminopyrine and erythromycin N-demethylase, ethoxycoumarin O-deethylase, and androstenedione 16 beta- and 15 alpha/6 beta hydroxylase activities; however, clorimazole did not induce aminopyrine N-demethylase activity irrespective of its marked increase in P450 content. Immunoblot analyses revealed that climbazole induced CYP2B1, 3A2 and 4A1. The present findings indicate that climbazole is a new potent inducer of hepatic microsomal P450 and drug-metabolizing enzymes like clorimazole, but it may have some differential mechanism(s) for these enzymes' induction in rat liver.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: N
authors.initials: N
authors.lastname: Ohshiro
authors.forename: T
authors.initials: T
authors.lastname: Sunagawa
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.forename: S
authors.initials: S
authors.lastname: Tokuyama
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000935:Antifungal Agents; D007093:Imidazoles; D003577:Cytochrome P-450 Enzyme System; C108286:climbazole; D010089:Oxidoreductases, N-Demethylating