RT Journal Article
SR Electronic
T1 Identification of [<sup>14</sup>C]Fluasterone Metabolites in Urine and Feces Collected from Dogs after Subcutaneous and Oral Administration of [<sup>14</sup>C]Fluasterone
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1089
OP 1097
DO 10.1124/dmd.108.023614
VO 37
IS 5
A1 Burgess, Jason P.
A1 Green, Jonathan S.
A1 Hill, Judith M.
A1 Zhan, Qiao
A1 Lindeblad, Matthew
A1 Lyubimov, Alexander
A1 Kapetanovic, Izet M.
A1 Schwartz, Arthur
A1 Thomas, Brian F.
YR 2009
UL http://dmd.aspetjournals.org/content/37/5/1089.abstract
AB The objective of this research was the identification of the metabolic profile of fluasterone, a synthetic derivative of dehydroepiandrosterone, in dogs treated orally or subcutaneously with [4-14C]fluasterone. Separation and characterization techniques used to identify the principal metabolites of fluasterone in urine and feces included high-performance liquid chromatography (HPLC), liquid scintillation spectrometry, HPLC/tandem mass spectrometry, and NMR. In urine, the majority of the radioactivity was present as two components that had apparent molecular weights consistent with their tentative identification as monoglucuronide conjugates of 4α-hydroxy-16α-fluoro-5-androsten-17β-ol and X(α or β)-4α-dihydroxy-16α-fluoro-5-androsten-17β-ol. The identification of the monoglucuronide conjugate of 4α-hydroxy-16α-fluoro-5-androsten-17β-ol was also supported by NMR data. In support of this identification, these metabolites were cleaved with glucuronidase enzyme treatment, which gave rise to components with molecular weights again consistent with the aglycones of a monohydroxylated, 17-keto reduced (dihydroxy) fluasterone metabolite and a dihydroxylated, 17-keto reduced (trihydroxy) fluasterone metabolite. In feces, nonconjugated material predominated. The primary metabolites eliminated in feces were the two hydroxy fluasterone metabolites arising from 17-reduction (16α-fluoro-5-androsten-17β-ol and 16α-fluoro-5-androsten-17α-ol) and 4α-hydroxy-16α-fluoro-5-androsten-17β-ol that was present in urine in glucuronide form. U.S. Government work not protected by U.S. copyright.