Halstenson C E, Wong M O, Johnson C A, Zimmerman S W, Onorato J J, Keane W F, Doepner M, Sia L, Tantillo K, Bansal S
Drug Evaluation Unit, Hennepin County Medical Center, Minneapolis, Minnesota 55404.
J Clin Pharmacol. 1994 Dec;34(12):1208-17. doi: 10.1002/j.1552-4604.1994.tb04733.x.
Tazobactam is a new derivative of penicillinic acid sulfone, which functions as an irreversible inhibitor of many beta-lactamases. The disposition of tazobactam M1 metabolite after intravenous (i.v.) infusion of 3 g of piperacillin/0.375 g of tazobactam was evaluated in 26 subjects with various degrees of renal impairment. Participants in the study were 18 subjects with creatinine clearances (ClCR) ranging from 7.4-41.8 mL/min, 4 subjects maintained on continuous ambulatory peritoneal dialysis (CAPD), and 4 subjects undergoing chronic hemodialysis (HD). The pharmacokinetic parameters of piperacillin and tazobactam were evaluated and were similar to previous reports. Tazobactam M1 metabolite maximum plasma concentration increased as renal function declined. The terminal elimination half-life and area under the plasma concentration-time curve of the tazobactam M1 metabolite increased as renal function declined. The mean rate of recovery of the tazobactam M1 metabolite in hemodialysate during a 3- to 4.2-hour HD session 1 hour after the i.v. infusion of piperacillin/tazobactam was 25.3%. However, when HD was performed at 36-48 hours after the i.v. infusion, 57.6% of the tazobactam dose was recovered as M1 metabolite, suggesting further conversion of tazobactam to M1 metabolite. Peritoneal dialysis removed 15.8% (n = 2) of the tazobactam dose as the M1 metabolite. Using a dose of 3 g of piperacillin/0.375 g of tazobactam, the predicted maximum steady-state plasma concentrations of the tazobactam M1 metabolite are 14.6 micrograms/mL, 34.8 micrograms/mL, and 48.8 micrograms/mL for subjects with ClCR 20-40 mL/min (every 6 hour dosing), ClCR < 20 mL/min (every 8 hour dosing), and on CAPD (every 12 hour dosing), respectively.
他唑巴坦是青霉素酸砜的一种新衍生物，它作为许多β-内酰胺酶的不可逆抑制剂发挥作用。在26名有不同程度肾功能损害的受试者中评估了静脉输注3克哌拉西林/0.375克他唑巴坦后他唑巴坦M1代谢物的处置情况。该研究的参与者包括18名肌酐清除率（ClCR）在7.4 - 41.8毫升/分钟之间的受试者、4名接受持续性非卧床腹膜透析（CAPD）的受试者以及4名接受慢性血液透析（HD）的受试者。评估了哌拉西林和他唑巴坦的药代动力学参数，其与先前报告相似。他唑巴坦M1代谢物的最大血浆浓度随肾功能下降而升高。他唑巴坦M1代谢物的末端消除半衰期和血浆浓度 - 时间曲线下面积随肾功能下降而增加。在静脉输注哌拉西林/他唑巴坦1小时后的3至4.2小时血液透析期间，血液透析液中他唑巴坦M1代谢物的平均回收率为25.3%。然而，当在静脉输注后36 - 48小时进行血液透析时，57.6%的他唑巴坦剂量以M1代谢物形式被回收，这表明他唑巴坦进一步转化为M1代谢物。腹膜透析以M1代谢物形式清除了15.8%（n = 2）的他唑巴坦剂量。使用3克哌拉西林/0.375克他唑巴坦的剂量，对于ClCR为20 - 40毫升/分钟（每6小时给药一次）、ClCR < 20毫升/分钟（每8小时给药一次）以及接受CAPD（每12小时给药一次）的受试者，他唑巴坦M1代谢物的预测最大稳态血浆浓度分别为14.6微克/毫升、34.8微克/毫升和48.8微克/毫升。
