Endocrinological effects of single daily ketoconazole administration in male beagle dogs.
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 17 alpha-hydroxyprogesterone, progesterone and 17 alpha, 20 alpha-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-17 alpha 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-17 beta 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.
D019326:17-alpha-Hydroxyprogesterone; D000284:Administration, Oral; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood*; D006854:Hydrocortisone / Q000097:blood*; D006908:Hydroxyprogesterones / Q000097:blood; D007654:Ketoconazole / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D011374:Progesterone / Q000097:blood*; D013739:Testosterone / Q000097:blood*; D013997:Time Factors
D006908:Hydroxyprogesterones; C007433:17,20-dihydroxy-4-pregnen-3-one; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D019326:17-alpha-Hydroxyprogesterone; D007986:Luteinizing Hormone; D007654:Ketoconazole; D006854:Hydrocortisone