Single and Multiple Dose Pharmacokinetic Evaluation of Flutamide in Normal Geriatric Volunteers

Abstract

Single dose and steady‐state pharmacokinetics of flutamide (F) and its active plasma metabolite, hydroxyflutamide (HF) were studied in twelve healthy geriatric volunteers administered 250 mg flutamide capsules on day 1 and 250 mg flutamide capsules three times a day on days 2 through 9. After oral administration, F was rapidly absorbed and metabolized. It was present in the plasma in small and variable concentrations, which precluded quantitative assessment of pharmacokinetic parameters for individual subjects. Steady‐state plasma concentrations were reached on or before Day 6. The mean steady state C_max (Day 9), 112.7 ng/ml, occurred at 1.3 hr. Pharmacokinetic analysis of mean data at steady‐state gave a distribution and elimination half‐life of 0.8 hr and 7.8 hours, respectively. The plasma levels for HF were much higher and less variable than F. The mean C_max for HF averaged 894 ng/ml at 2.7 hours after a single dose and 1719 ng/ml (Day 9) at 1.9 hr after multiple doses. The distribution and elimination half‐lives of HF at steady‐state were 1.9 and 9.6 hours, respectively. The steady‐state HF plasma concentrations were also achieved on or before Day 6 and were approximately twice those obtained after a single dose. From this study, it has been demonstrated that the pharmacokinetics of F and HF do not change appreciably upon multiple dosing of 250 mg F capsule given three times a day.