Pharmacokinetics of flutamide in patients with renal insufficiency

Aims The aim of this study was to determine the pharmacokinetic parameters of flutamide, a nonsteroidal antiandrogenic compound, and its pharmacologic ally active metabolite, hydroxyflutamide, in renal insufficiency. Haemodial ysis (HD) clearance of flutamide and hydroxyflutamide was also determined. Methods Pharmacokinetic parameters were assessed for flutamide and hydroxyf lutamide in 26 male subjects with normal renal function (creatinine clearan ce by 24 h urine collection, CLcr, greater than 80 ml min(-1) 1.73 m(-2); n = 6) or reduced renal function; CLcr = 50-80 (n = 7), 30-49 (n = 3), 5-29 (n = 4), and <5 ml min(-1) 1.73 m(-2)-HD (n = 6), following a single, oral 250 mg flutamide dose. Subjects undergoing HD received a second 250 mg dose of flutamide 4 h prior to HD; blood and dialysate were collected during HD to determine dialysability of flutamide and hydroxyflutamide. Results C-max, t(max), AUC, t(1/2), and renal clearance of flutamide and hy droxyflutamide did not differ between groups. Less than 1% of the dose appe ared in dialysate as hydroxyflutamide. No serious adverse events were obser ved. Conclusions Renal function did not affect flutamide nor hydroxyflutamide di sposition. HD did not alter hydroxyflutamide pharmacokinetics. Dosing adjus tments for renal impairment or HD are not indicated for flutamide.