Plasma concentrations and effect on testosterone metabolism after single doses of MK-0434, a steroid 5 alpha-reductase inhibitor, in healthy subjects.
A four-period, two-panel, single-rising-dose study (0.1-100 mg) was conducted in healthy males to investigate the pharmacodynamics, tolerability and pharmacokinetics of MK-0434, a steroid 5 alpha-reductase inhibitor. MK-0434 was associated with a significant reduction in dihydrotestosterone, which was maximal at 24 h and maintained through 48 h post treatment. The maximum reduction was approximately 50% and occurred at all doses above 5 mg (10, 25, 50 and 100 mg). MK-0434 appeared to have no effect on serum testosterone at these single doses. Rising single doses of MK-0434 were associated with an increase in Cmax and AUC but the changes were less than proportional to dose, most likely due to nonlinear absorption. MK-0434 given in single doses up to 100 mg was without significant adverse effects in healthy male volunteers. In summary, MK-0434 is a well-tolerated, potent, orally active 5 alpha-reductase inhibitor in man.
Van Hecken
A
A
Department of Pharmacology, University of Leuven, School of Medicine, Belgium.
Depré
M
M
Schwartz
J I
JI
Tjandramaga
T B
TB
Winchell
G A
GA
De Lepeleire
I
I
Ng
J
J
De Schepper
P J
PJ
D058891:5-alpha Reductase Inhibitors; D000328:Adult; D013196:Dihydrotestosterone / Q000097:blood*; D018120:Finasteride / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D006801:Humans; D008297:Male; D012016:Reference Values
C088478:17 beta-benzoyl-4-aza-5 alpha-androst-1-ene-3-one; D058891:5-alpha Reductase Inhibitors; D013196:Dihydrotestosterone; D018120:Finasteride