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: [GRAPHICS] where joint fitting of three dose levels yielded k(in)(0) = 28% change/hour, k(out) = 0.28 hour(-1), IC50 = 0.012 ng/ml, and E(max) = 0.7. The modification of a previous model with the maximum partial effect factor, E(max), may be useful in characterizing the pharmacodynamics of drugs with similar indirect mechanisms.