title: Metabolism of osaterone acetate in dogs and humans.
abstract: Osaterone acetate (17 alpha-acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,20-dione; OA) is a steroidal antiandrogen. In order to clarify the species differences, metabolites of OA were examined in plasma, urine, and feces of dogs and humans after oral administration of OA. Eleven metabolites in plasma, urine, and feces were identified by their spectral properties and comparison to appropriate standards. The primary routes of OA metabolism involve 11 beta-, 15 beta- and 21-hydroxylation, 17 alpha-deacetylation, and dechlorination. Other metabolites arise from combinations of these pathways to form multiple oxidized metabolites. All metabolites observed in humans occurred in dogs. 11 beta-Hydroxylated metabolites (11 beta-OH OA and 11-oxo OA) were found in the plasma and urine of dogs, but there was no evidence of their presence in humans. 11 beta-Hydroxylation of exogenous steroids represents a distinctive biotransformation pathway.
authors.affiliation: Safety & Pharmacokinetics Research Department, Teikoku Hormone Mfg. Co. Ltd., 1604 Shimosakunobe, Takatsu-ku, Kawasaki-shi, Kanagawa 213-8522, Japan. minato-k@teioku-hormone.co.jp
authors.forename: Kouichi
authors.initials: K
authors.lastname: Minato
authors.forename: Seijirou
authors.initials: S
authors.lastname: Honma
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Takao
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000107:Acetylation; D000284:Administration, Oral; D000726:Androgen Antagonists / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D000818:Animals; D002715:Chlormadinone Acetate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D004285:Dogs; D005243:Feces / Q000737:chemistry; D006801:Humans; D006900:Hydroxylation; D015394:Molecular Structure; D013045:Species Specificity; D013258:Steroids, Chlorinated / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000726:Androgen Antagonists; D013258:Steroids, Chlorinated; D002715:Chlormadinone Acetate; C069297:osaterone acetate