Glue P, Sulowicz W, Colucci R, Banfield C, Pai S, Lin C, Affrime M B
Department of Clinical Pharmacology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033-0539, USA.
Br J Clin Pharmacol. 1997 Jul;44(1):91-3. doi: 10.1046/j.1365-2125.1997.00619.x.
The purpose of this study was to evaluate the effects of renal impairment on the single-dose pharmacokinetics of the antiepileptic felbamate.
Twelve subjects with three levels of renal dysfunction (creatinine clearance > 30-80, > 10-30 or 5-10 m min(-1)) and four controls with normal renal function (creatinine clearance > 80 ml min(-1) were studied). Plasma and urine samples were obtained for 144 h following administration of a single 1200 mg dose.
Compared with controls, apparent total body clearance, renal clearance and urinary excretion of felbamate were decreased, and half-life, Cmax and AUC values were increased in subjects with renal dysfunction. The magnitude of these changes was associated with the degree of renal dysfunction. Nonrenal clearance and apparent volume of distribution values were also lower in renal dysfunction subjects, but there was no association between the extent of these changes and degree of renal dysfunction. Renal clearance of felbamate accounted for approximately 30% of apparent total body clearance in the control group and from 9-22% in the renal failure patients. Renal clearance of felbamate was significantly correlated with creatinine clearance (r = 0.75; P< 0.001).
These data suggest that initial dosage and titration of felbamate may require adjustment in patients with renal dysfunction.
本研究旨在评估肾功能损害对抗癫痫药物非氨酯单剂量药代动力学的影响。
研究了12名具有三个肾功能水平（肌酐清除率>30 - 80、>10 - 30或5 - 10 ml·min⁻¹）的受试者以及4名肾功能正常（肌酐清除率>80 ml·min⁻¹）的对照者。单次给予1200 mg剂量后，采集144小时的血浆和尿液样本。
与对照组相比，肾功能不全受试者的非氨酯表观全身清除率、肾清除率和尿排泄量降低，半衰期、Cmax和AUC值升高。这些变化的幅度与肾功能不全的程度相关。肾功能不全受试者的非肾清除率和表观分布容积值也较低，但这些变化的程度与肾功能不全的程度之间无关联。在对照组中，非氨酯的肾清除率约占表观全身清除率的30%，在肾衰竭患者中为9% - 22%。非氨酯的肾清除率与肌酐清除率显著相关（r = 0.75；P < 0.001）。
这些数据表明，肾功能不全患者可能需要调整非氨酯的初始剂量和滴定剂量。
