Chimata M, Nagase M, Suzuki Y, Shimomura M, Kakuta S
First Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Antimicrob Agents Chemother. 1993 Feb;37(2):229-33. doi: 10.1128/AAC.37.2.229.
The pharmacokinetics of meropenem were studied after intravenous infusion in 13 patients grouped according to the impairment of their renal function. Creatinine clearance (CLCR) was greater than 50, 50 to 30, and less than 30 ml/min in groups I, II, and III, respectively. Two other groups, groups IV and V, each comprising four patients with end-stage renal disease (CLCR, < 5 ml/min), were also studied, the former on days off of hemodialysis and the latter on days of hemodialysis. The elimination half-lives of meropenem were 1.54 +/- 0.70 h in group I patients, 3.36 +/- 1.02 h in group II patients, and 5.00 +/- 1.05 h in group III patients. Cumulative urinary excretion accounted for 48.5% of the dose in group I patients and decreased progressively with a decline in renal function. Hemodialysis shortened the elimination half-life of meropenem from 7.0 h to 2.9 h. H-4295, the main metabolite of meropenem, had a peak level in plasma of 0.5 to 1.0 h in patients with renal failure. The level of H-4295 decreased with hemodialysis. The dosing interval of meropenem should be prolonged in a regular proportion to the decline in CLCR (12 h in group II patients and 24 h in group III patients). In patients receiving hemodialysis, dosing after each hemodialysis session is recommended.
对13例根据肾功能损害分组的患者静脉输注美罗培南后进行了药代动力学研究。I、II和III组患者的肌酐清除率（CLCR）分别大于50、50至30以及小于30 ml/min。还对另外两组，即IV组和V组进行了研究，每组包括4例终末期肾病患者（CLCR＜5 ml/min），前者在血液透析日之外，后者在血液透析日进行研究。美罗培南的消除半衰期在I组患者中为1.54±0.70小时，在II组患者中为3.36±1.02小时，在III组患者中为5.00±1.05小时。I组患者的累积尿排泄量占给药剂量的48.5%，并随肾功能下降而逐渐减少。血液透析使美罗培南的消除半衰期从7.0小时缩短至2.9小时。美罗培南的主要代谢产物H - 4295在肾衰竭患者血浆中的峰值水平出现在0.5至1.0小时。H - 4295的水平随血液透析而降低。美罗培南的给药间隔应按CLCR下降的比例相应延长（II组患者为12小时，III组患者为24小时）。对于接受血液透析的患者，建议在每次血液透析后给药。
