Anjum S, Swan S K, Lambrecht L J, Radwanski E, Cutler D L, Affrime M B, Halstenson C E
Total Renal Research Institute, Division of Nephrology, Hennepin County Medical Center, Minneapolis, MN 55415, USA.
Br J Clin Pharmacol. 1999 Jan;47(1):43-7. doi: 10.1046/j.1365-2125.1999.00831.x.
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.
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.
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.
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.
本研究旨在确定非甾体抗雄激素化合物氟他胺及其药理活性代谢产物羟基氟他胺在肾功能不全患者中的药代动力学参数。同时也测定了氟他胺和羟基氟他胺的血液透析（HD）清除率。
对26名男性受试者进行了氟他胺和羟基氟他胺的药代动力学参数评估，这些受试者的肾功能正常（通过24小时尿液收集测定肌酐清除率，CLcr，大于80 ml·min⁻¹·1.73 m⁻²；n = 6）或肾功能降低；CLcr = 50 - 80（n = 7）、30 - 49（n = 3）、5 - 29（n = 4）以及<5 ml·min⁻¹·1.73 m⁻² - HD（n = 6），所有受试者均单次口服250 mg氟他胺。接受血液透析的受试者在透析前4小时接受第二剂250 mg氟他胺；在血液透析期间收集血液和透析液，以确定氟他胺和羟基氟他胺的透析性。
各组之间氟他胺和羟基氟他胺的Cmax、tmax、AUC、t1/2和肾清除率无差异。透析液中以羟基氟他胺形式出现的剂量不到1%。未观察到严重不良事件。
肾功能不影响氟他胺和羟基氟他胺的处置。血液透析不会改变羟基氟他胺的药代动力学。氟他胺无需因肾功能损害或血液透析而调整剂量。
