Pharmacodynamic modeling of finasteride, a 5 alpha-reductase inhibitor

Finasteride is a 4-azasteroid inhibitor of one isoenzyme of 5 alpha-reductases that converts testosterone to dihydrotestosterone (DHT). We characterized the time course of DHT concentrations. The following model was used to assess DHT pharmacodynamics: [formula: see text] where joint fitting of three dose levels yielded kin0 = 28% change/hour, kout = 0.28 hour-1, IC50 = 0.012 ng/ml, and Emax = 0.7. The modification of a previous model with the maximum partial effect factor, Emax, may be useful in characterizing the pharmacodynamics of drugs with similar indirect mechanisms.