Description:
<jats:title>Abstract</jats:title><jats:p>The objective of this study was to estimate the minimum in vivo effective oral dose and duration of action of the competitive 5α‐reductase inhibitor MK‐906, a 4‐azasteroid, in humans. Plasma dihydrotestosterone (DHT), 5α‐androstane‐3α, 17β‐diol (AD), and its glucuronide (ADG), as well as urinary androsterone (A) and 5α‐pregnane‐3α, 11β, 17α, 21‐tetrol‐20‐one (aH<jats:sub>4</jats:sub>F) were determined in 54 healthy young men before and up to 7 days after a single morning dose of the compound. Twenty‐four hours after a single 5‐to 40‐mg dose (n = 24), plasma DHT levels decreased by a mean of ± 65%, with slow recovery of DHT levels. Seven days later, DHT remained decreased by ± 15%. Plasma AD levels decreased to a similar degree, whereas ADG levels decreased by about 75%, indicating inhibition of target tissue 5α‐reductase. Testosterone levels did not show any significant variations. The A as well as aH<jats:sub>4</jats:sub>F excretion in the 24‐hour urine test following drug administration decreased by 65%, indicating inhibition of the hepatic 5α‐reductase. After a single dose of 1.5 or 0.5 mg, DHT levels decreased by 50% 24 hours after administration, returning to normal within 5–7 days; at this dose, urinary A and aH<jats:sub>4</jats:sub>F excretion decreased by 50%. A single dose of 0.2 mg appeared to be slightly active as a 5α‐reductase inhibitor, but no statistically significant effect on DHT levels was observed after administration of a single 0.04‐mg dose. It is concluded that MK‐906 is a highly effective 5α‐reductase inhibitor in vivo. The effect on plasma DHT lasts for several days after administration of a single oral dose. The data suggest that both hepatic and extrasplanchnic 5α‐reductases are inhibited.</jats:p>