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 co nducted in healthy males to investigate the pharmacodynamics, tolerabi lity and pharmacokinetics of MK-0434, a steroid 5 alpha-reductase inhi bitor. MK-0434 was associated with a significant reduction in dihydrot estosterone, which was maximal at 24 h and maintained through 48 h pos t 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 ha ve no effect on serum testosterone at these single doses. Rising singl e doses of MK 0434 were associated with an increase in C-max and AUC b ut 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 sum mary, MK-0434 is a well-tolerated, potent, orally active 5 alpha-reduc tase inhibitor in man.