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Ketoconazole inhibition of progesterone oxidation by the rabbit



Ketoconazole inhibition of progesterone oxidation by the rabbit



Biochemical Pharmacology 37(19): 3647-3652



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.

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Accession: 001625779

Download citation: RISBibTeXText

PMID: 3178878

DOI: 10.1016/0006-2952(88)90397-8


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