Endocrinological effects of single daily ketoconazole administration in male beagle dogs

Abstract

Abstract. Some endocrinological effects of single daily oral administration of 150 mg ketoconazole for 15 days were investigated in 4 male beagle dogs. Plasma testosterone fell markedly within 3–4 h and then progressively returned to control concentrations by 10 h after drug administration. On the other hand, plasma 17α-hydroxyprogesterone, progesterone and 17α,20α-dihydroxyprogesterone increased within 3–10 h before returning to basal values after 24 h. Plasma LH did not rise significantly though some high individual levels were noted. Plasma cortisol and oestradiol-17α levels were not significantly modified by the treatment. These results confirm that a high therapeutic dose of ketoconazole, given orally once a day, transiently inhibits in vivo the 17–20 lyase enzyme of the testis, without modifying basal cortisol and oestradiol-17β plasma concentrations and that enzymatic inhibition still occurs after daily treatment for up to 2 weeks but remains transient and parallels the resorption profile of the drug so that normal plasma testosterone levels are observed from 10 to 24 h after drug intake. However, permanent inhibition of androgen biosynthesis might be obtained by the administration of high doses of ketoconazole given several times a day.