Johnson C A, Halstenson C E, Kelloway J S, Shapiro B E, Zimmerman S W, Tonelli A, Faulkner R, Dutta A, Haynes J, Greene D S
University of Wisconsin Hospital and Clinics, Madison.
Clin Pharmacol Ther. 1992 Jan;51(1):32-41. doi: 10.1038/clpt.1992.5.
Tazobactam is an irreversible inhibitor of many beta-lactamases. In combination with piperacillin, tazobactam exhibits synergy against many beta-lactamase-producing bacteria. The pharmacokinetics of piperacillin and tazobactam were evaluated in eight normal volunteers and in 52 patients with renal dysfunction. Plasma and urine were obtained for up to 30 hours after an infusion of piperacillin and tazobactam (3 and 0.375 gm, respectively). Dialysate samples were collected from patients undergoing dialysis. Piperacillin and tazobactam concentrations were determined by high-performance liquid chromatography. Noncompartmental methods were used for pharmacokinetic analysis. Piperacillin and tazobactam total body clearance, area under the curve, and terminal elimination rate correlated with renal function. Hemodialysis removed 31% and 39% of piperacillin and tazobactam, respectively. During continuous ambulatory peritoneal dialysis, 5.5% of the piperacillin and 10.7% of the tazobactam was recovered in the dialysate over 28 hours. Peak plasma concentrations of both drugs increased minimally with decreasing creatinine clearance. Dosage alterations for creatinine clearance values less than 40 ml/min are recommended.
他唑巴坦是多种β-内酰胺酶的不可逆抑制剂。与哌拉西林联合使用时，他唑巴坦对许多产β-内酰胺酶的细菌具有协同作用。在8名正常志愿者和52名肾功能不全患者中评估了哌拉西林和他唑巴坦的药代动力学。在输注哌拉西林和他唑巴坦（分别为3克和0.375克）后长达30小时采集血浆和尿液样本。从接受透析的患者中收集透析液样本。通过高效液相色谱法测定哌拉西林和他唑巴坦的浓度。采用非房室方法进行药代动力学分析。哌拉西林和他唑巴坦的总体清除率、曲线下面积和终末消除率与肾功能相关。血液透析分别清除了31%的哌拉西林和39%的他唑巴坦。在持续性非卧床腹膜透析期间，28小时内透析液中回收了5.5%的哌拉西林和10.7%的他唑巴坦。随着肌酐清除率降低，两种药物的血浆峰浓度仅有轻微升高。建议对肌酐清除率低于40 ml/min的值调整剂量。
