Pharmacodynamics and tolerability of L-654,066, a steroid 5 alpha-reductase inhibitor, in men.
A four-period, two-panel single rising-dose study (0.1 to 100 mg) was conducted in healthy men to investigate the pharmacodynamics and tolerability of L-654,066, a steroid 5 alpha-reductase inhibitor. Within each panel, six subjects received L-654,066 and two subjects received placebo at each dose level; the placebo subjects changed between periods so that each subject received placebo once. Testosterone and dihydrotestosterone were measured in serum at 0, 4, 24, and 48 hours after each treatment. L-654,066 was associated with a significant reduction in serum dihydrotestosterone concentrations, which was maximal at 48 hours after dose. Forty-eight hours after treatment, mean percentage of inhibition was 24% and 39% for the 0.1 and 0.5 mg doses, respectively, and ranged from 50% to 65% at doses from 1 to 25 mg and from 70% to 75% at doses from 50 to 100 mg. Testosterone serum levels did not show any significant difference between the various treatments, including placebo.
Depré
M
M
Department of Pharmacology, Catholic University of Leuven, Belgium.
Meeter
C
C
Van Hecken
A
A
Laskin
O L
OL
Buntinx
A
A
De Schepper
P J
PJ
D058891:5-alpha Reductase Inhibitors; D000328:Adult; D001378:Azasteroids / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D012016:Reference Values; D013739:Testosterone / Q000097:blood
D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D013196:Dihydrotestosterone; C077586:(5alpha)-23-methyl-4-aza-21-norchol-1-ene-3,20-dione; D013739:Testosterone