@article {Khan360, author = {W A Khan and C Kuhn and H F Merk and S S Park and H V Gelboin and D R Bickers and H Mukhtar}, title = {Isozyme-specific monoclonal antibody-directed assessment of induction of hepatic cytochrome p-450 by clotrimazole.}, volume = {17}, number = {4}, pages = {360--364}, year = {1989}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Clotrimazole, an N-substituted imidazole widely used as an antifungal agent, has been shown to both inhibit and induce hepatic cytochrome P-450 and related monooxygenase activities. In this study the profile of hepatic cytochrome P-450 isozyme(s) induced by clotrimazole treatment of male Sprague-Dawley rats was investigated. Clotrimazole administration (100 mg/kg, daily for 4 days, ig) resulted in 86\% induction of spectrally detectable cytochrome P-450 in hepatic microsomes. In these microsomes 7-ethoxycoumarin O-deethylase (126\%), aminopyrine N-demethylase (176\%), benzphetamine N-demethylase (117\%), p-nitrophenol hydroxylase (89\%), and 7-ethoxyresorufin O-deethylase (62\%) activities were significantly induced, whereas aryl hydrocarbon hydroxylase activity remained unchanged. Characterization of cytochrome P-450 isozyme(s) in hepatic microsomes prepared from clotrimazole-treated animals was based on the immunoreactivity of these microsomes with highly specific monoclonal antibodies (MAbs) raised against 3-methylcholanthrene-specific P-450 (MAb 1-7-1), phenobarbital-specific P-450 (MAb 2-66-3), pregnenolone-16 alpha-carbonitrile-specific P-450 (MAb C2), and ethanol-inducible P-450 (MAb 1-98-1). Western blot analysis of hepatic microsomes prepared from clotrimazole-treated animals with MAb 2-66-3, MAb 1-98-1, and MAb C2 revealed strong immunoreactive bands, whereas moderate reactivity was observed with MAb 1-7-1. MAb 2-66-3 significantly inhibited 7-ethoxycoumarin O-deethylase activity 45\%), whereas MAb 1-7-1 moderately inhibited 7-ethoxyresorufin O-deethylase activity (-30\%) in clotrimazole-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/17/4/360}, eprint = {https://dmd.aspetjournals.org/content/17/4/360.full.pdf}, journal = {Drug Metabolism and Disposition} }