Studies on the Metabolic Fate of Flutamide (3) : Absorption, Distribution and Excretion following Consecutive Oral Administration in Rats

Abstract

Pharmacokinetic studies of Flutamide were performed in rats. Blood and plasma levels, tissue distribution and excretion of Flutamide were examined during and after the consecutive oral administration of ¹⁴C-Flutamide at a daily dose of 5 mg/kg for 21 days.
1. The blood levels of radioactivity at 24 hr after daily dosing increased with the number of dose, reaching the steady state on day 16.
2. The radioactivity was well distributed in all the tissues following the consecutive oral doses. The concentrations in the blood, small intestine, kidney, spleen, preputinal gland, stomach and the liver were 4.4 ?? 6.0 times higher than those after a single dosing, and that in the other tissues were 2.6 ?? 3.8 times higher. The radioactivity in most tissues after the final dosing was eliminated slowly from the tissues.
3. Excretion rates of radioactivity into urine and feces were 68.2 and 24.6% at 120 hr after the final dosing, respectively. These were almost constant duringthe consecutive oral doses. Residual radioactivity in rats was 0.6% of the total doses.