title: Pharmacodynamics of MK-0963, a new 5 alpha-reductase inhibitor: effects on serum androgen concentrations.
abstract: The hormonal effects after a 10-day administration of a 4-azasteroid inhibitor of 5 alpha-reductase, MK-0963 (previously L-654,066), were evaluated in 35 healthy male volunteers in an increasing-dose, five-panel design. Marked suppression of serum dihydrotestosterone was observed after the once-daily administration at each active dose level (placebo, 0.1, 0.5, 1.0, 10, and 25 mg). Maximum dihydrotestosterone suppression occurred at doses greater than or equal to 10 mg. The mean percentage (+/- SE) decreases in dihydrotestosterone at 24 hours after the last dose in the groups treated with the 10 and 25 mg doses were 78% +/- 4.9% and 80% +/- 2.9%, respectively. The 25 mg dose maintained a dihydrotestosterone suppression of at least 70% for more than 6 days after the last dose. No consistent changes in serum testosterone were noted. This study shows that administration of multiple doses of MK-0963 results in a substantial suppression of serum dihydrotestosterone with no consistent influence on serum testosterone concentrations.
authors.affiliation: Department of Clinical Pharmacology and Biostatistics, Merck Research Laboratories, Rahway, NJ 07065-0914.
authors.forename: J I
authors.initials: JI
authors.lastname: Schwartz
authors.forename: O L
authors.initials: OL
authors.lastname: Laskin
authors.forename: C A
authors.initials: CA
authors.lastname: Meeter
authors.forename: P M
authors.initials: PM
authors.lastname: Patterson
authors.forename: S H
authors.initials: SH
authors.lastname: Schneider
authors.forename: K C
authors.initials: KC
authors.lastname: Lasseter
authors.forename: J R
authors.initials: JR
authors.lastname: Seibold
mesh_terms: D058891:5-alpha Reductase Inhibitors; D000328:Adult; D000728:Androgens / Q000097:blood*; D001378:Azasteroids / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D013739:Testosterone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000097:blood
chemical_list: D058891:5-alpha Reductase Inhibitors; D000728:Androgens; D001378:Azasteroids; C077586:(5alpha)-23-methyl-4-aza-21-norchol-1-ene-3,20-dione; D013739:Testosterone; C013915:boldenone