Pharmacokinetics of flutamide in patients with renal insufficiency.

Abstract

AIMS:

The aim of this study was to determine the pharmacokinetic parameters of flutamide, a nonsteroidal antiandrogenic compound, and its pharmacologically active metabolite, hydroxyflutamide, in renal insufficiency. Haemodialysis (HD) clearance of flutamide and hydroxyflutamide was also determined.

METHODS:

Pharmacokinetic parameters were assessed for flutamide and hydroxyflutamide in 26 male subjects with normal renal function (creatinine clearance 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:

Cmax, tmax, AUC, t1/2, and renal clearance of flutamide and hydroxyflutamide did not differ between groups. Less than 1% of the dose appeared in dialysate as hydroxyflutamide. No serious adverse events were observed.

CONCLUSIONS:

Renal function did not affect flutamide nor hydroxyflutamide disposition. HD did not alter hydroxyflutamide pharmacokinetics. Dosing adjustments for renal impairment or HD are not indicated for flutamide.

• Authors: S Anjum, S K Swan, L J Lambrecht, E Radwanski, D L Cutler, M B Affrime, C E Halstenson
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 47 Issue 1 Pg. 43-7 (Jan 1999) ISSN: 0306-5251 [Print] England
• PMID: 10073738 (Publication Type: Journal Article)

Chemical References

• Androgen Antagonists
• hydroxyflutamide
• Flutamide

Topics

• Androgen Antagonists (adverse effects, pharmacokinetics)
• Area Under Curve
• Flutamide (adverse effects, analogs & derivatives, pharmacokinetics)
• Half-Life
• Humans
• Male
• Middle Aged
• Renal Dialysis
• Renal Insufficiency (metabolism)