Studies on the Metabolic Fate of Flutamide (1) : Plasma Concentration after Single Administration and Protein Binding in Rats

Abstract

Pharmacokinetic studies of plasma levels of Flutamide, a pure antiandrogen agent for prostate cancer, were performed in rats after a single oral and intravenous administration at doses of 5 and 10 mg/kg, respectively.
1. Hydroxy-flutamide (OH-Flutamide) was a major metabolite in rat plasma after oral and intravenous administration of Flutamide.
2. Plasma concentration of Flutamide and OH-Flutamide reached C_max of 34.1 ng/ml (T_max: 0.5 hr) and 495.8 ng/ml (T_max: 2 hr) after a single oral administration of Flutamide at a dose of 5 mg/kg to male rats, and then decreased with half-lives of 0.45 and 3.8 hr, respectively. The C_max and AUC increased proportionally to the administration doses.
3. After an intravenous injection of Flutamide to rats, plasma levels of Flutamide and OH-Flutamide decreased with half-lives of 0.46 hr and 4.1 hr, respectively.