The effects of ketoconazole on testosterone production and normal and malignant androgen dependent tissues of the adult rat.
Ketoconazole is a potent inhibitor of the P450 series of enzymes that are essential for the production of androgens. In order to determine the effects of ketoconazole on androgen production and androgen dependent tissues in the rat, adult male rats were administered varying doses of ketoconazole every 12 hours. Serum testosterone declined to unmeasurable levels at ketoconazole doses of greater than 4 mg. This dose was sufficient to completely inhibit the testosterone surge induced by the administration of a potent luteinizing releasing hormone agonist. The ventral prostate weight of normal rats and the volume of the Dunning R3327H androgen dependent prostatic cancer declined at the same rate in animals treated with ketoconazole or castration. Ketoconazole may be an effective agent to treat androgen dependent diseases.
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D002369:Castration; D003864:Depression, Chemical; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D006207:Half-Life; D007654:Ketoconazole / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D016729:Leuprolide; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000097:blood*
D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D016729:Leuprolide; D007654:Ketoconazole