Pharmacokinetics and pharmacodynamics of FK143, a nonsteroidal inhibitor of steroid 5α-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 dihydrotestosterone levels as an index for pharmacologic effects, The area under the plasma concentration-time curve from aero to infinity [AUC(0-infinity)] and maximum plasma concentration [C-max] were increased dose proportionally after oral administration (100 to 500 mg) while subjects were in the fed state, The AUC(0-infinity) and C-max after 500 mg oral administration during fed conditions were significantly larger than those during the fasted state, suggesting an increase of the absorption of FK143, Dihydrotestosterone concentrations after a single administration of FK143 (100 to 500 mg) during fed conditions decreased to about 65% of predose values and thereafter slowly recovered to the same levels as predose values at 168 hours, A combined pharmacokinetic-pharmacodynamic model was constructed with use of changes in dihydrotestosterone concentrations, The pharmacokinetic-pharmacodynamic profiles of FK143 after repeated administration were predictable with use of the pharmacokinetic-pharmacodynamic parameters obtained after a single administration of FK143.