Pharmacokinetics of cyproterone acetate and its main metabolite 15 beta-hydroxy-cyproterone acetate in young healthy women.
Cyproterone acetate (CPA) and 15 beta-hydroxy-cyproterone acetate (15 beta-OH-CPA) have been quantitated in human plasma by a selective, automated HPLC assay in 8 young female subjects. Subjects received a single oral dose of 100 mg CPA and four weeks later, a single intramuscular dose of 300 mg CPA. Plasma levels in seven subjects could be evaluated pharmacokinetically. After intramuscular administration maximum CPA serum levels of 191 +/- 49 ng/ml were reached between 2 and 3 days. Postmaximal levels declined with a half-life of 4.3 +/- 0.7 days. After oral administration maximal serum levels of 255 +/- 110 ng/ml were measured between 2 and 3 h. CPA levels decayed biphasically with a terminal half-life of 3.6 +/- 1.3 days. Bioavailability after oral administration was nearly complete (88 +/- 20%). Metabolite levels were below CPA levels until 4 days (i.m.) and 6 h (p.o.) and exceeded CPA levels later on. 15 beta-OH-CPA levels declined with half-lives similar to those of corresponding CPA levels, indicating that terminal half-life of the metabolite in serum reflects its rate of formation rather than its rate of elimination. Areas under the metabolite serum level curves after intramuscular and oral administration were 10 to 15% higher than the corresponding areas for unchanged CPA. Since CPA and 15 beta-OH-CPA contribute to the antiandrogenetic efficacy there is good reason to assume that the intramuscular administration of CPA might be equally effective in the therapeutical use as the oral administration.
Huber
J
J
First Department of Obstetrics and Gynecology, University of Vienna, Austria.
Zeillinger
R
R
Schmidt
J
J
Täuber
U
U
Kuhnz
W
W
Spona
J
J
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003534:Cyproterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D017373:Cyproterone Acetate / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular
C045999:15-hydroxycyproterone acetate; D017373:Cyproterone Acetate; D003534:Cyproterone