Single and multiple dose pharmacokinetic evaluation of flutamide in normal geriatric volunteers.
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 Cmax (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 Cmax 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.
Radwanski
E
E
Department of Drug Metabolism and Pharmacokinetics Schering Corporation, Bloomfield, New Jersey 07003.
Perentesis
G
G
Symchowicz
S
S
Zampaglione
N
N
D000284:Administration, Oral; D000368:Aged; D000813:Anilides / Q000493:pharmacokinetics*; D001682:Biological Availability; D002849:Chromatography, Gas; D005485:Flutamide / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male
D000813:Anilides; C014290:hydroxyflutamide; D005485:Flutamide