Pharmacodynamics and tolerability of L‐654,066, a steroid 5α‐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 5α‐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. Clinical Pharmacology and Therapeutics (1992) 52, 409–412; doi: 10.1038/clpt.1992.163