Ketoconazole inhibition of progesterone oxidation by the rabbit.
Ketoconazole, a known cytochrome P-450 inhibitor, inhibited both progesterone ring hydroxylation and side-chain oxidation to steroidal acids. Progesterone 21 6 beta- and 16 alpha-hydroxylase activities of rabbit liver microsomes were inhibited 50% by ketoconazole at concentrations between 10(-5) and 10(-4) M. Steroid acid formation was similarly inhibited at a 10(-5) M concentration. Ketoconazole administration to rabbits produced a significant reduction in the urinary excretion of acidic metabolites of [3H]deoxycorticosterone and [14C]progesterone by approximately 50 and 75% respectively. The differential effect of ketoconazole in vivo may indicate that more than one acidic metabolite pathway may be operative.
Senciall
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IR
Medical School, Memorial University of Newfoundland, St. John's, Canada.
Rahal
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SR
Roberts
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D000818:Animals; D003900:Desoxycorticosterone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007654:Ketoconazole / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D011374:Progesterone / Q000378:metabolism*; D011817:Rabbits; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors
D003900:Desoxycorticosterone; D011374:Progesterone; D013250:Steroid Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; D007654:Ketoconazole