PHARMACOKINETICS AND PHARMACODYNAMICS OF FK143, A NONSTEROIDAL INHIBITOR OF STEROID 5-ALPHA-REDUCTASE, IN HEALTHY-VOLUNTEERS

The pharmacokinetics and pharmacodynamics of FK143, a new nonsteroidal inhibitor of steroid 5 alpha-reductase, were investigated in healthy volunteers, with use of plasma FK143 concentrations and serum dihydrot estosterone levels as an index for pharmacologic effects, The area und er the plasma concentration-time curve from aero to infinity [AUC(0-in finity)] and maximum plasma concentration [C-max] were increased dose proportionally after oral administration (100 to 500 mg) while subject s were in the fed state, The AUC(0-infinity) and C-max after 500 mg or al administration during fed conditions were significantly larger than those during the fasted state, suggesting an increase of the absorpti on of FK143, Dihydrotestosterone concentrations after a single adminis tration of FK143 (100 to 500 mg) during fed conditions decreased to ab out 65% of predose values and thereafter slowly recovered to the same levels as predose values at 168 hours, A combined pharmacokinetic-phar macodynamic model was constructed with use of changes in dihydrotestos terone concentrations, The pharmacokinetic-pharmacodynamic profiles of FK143 after repeated administration were predictable with use of the pharmacokinetic-pharmacodynamic parameters obtained after a single adm inistration of FK143.