Mouton J W, van den Anker J N
Department of Clinical Microbiology, Erasmus University, Rotterdam, The Netherlands.
Clin Pharmacokinet. 1995 Apr;28(4):275-86. doi: 10.2165/00003088-199528040-00002.
Meropenem is a recently developed carbapenem antibiotic, similar to imipenem, with a wide spectrum of activity against Gram-positive and Gram-negative bacteria. In comparison with imipenem, meropenem is relatively stable to hydrolysis by the enzyme dehydropeptidase I (DHP-I), thus precluding the need for coadministration with an inhibitor of DHP-I, such as cilastatin. Furthermore, meropenem may be less nephrotoxic and neurotoxic than imipenem. Plasma meropenem concentrations reach a peak (Cmax) of approximately 30 mg/L after administration of a standard dose of 1 g intravenously. The elimination half-life (t1/2) is approximately 1 hour, and the area under the plasma concentration-time curve increases linearly in a dose-related manner. The volume of distribution is 21L, indicating predominantly extracellular distribution. Meropenem distributes partly into cerebrospinal fluid. The drug is eliminated both by metabolism and excretion. In normal volunteers, up to 70% is recovered in urine, and the remainder is accounted for by a beta-lactam ring-opened form of the compound, ICI 213689. The t1/2 of meropenem is prolonged in patients with renal insufficiency and correlates well with creatinine clearance. Dosage adjustments in people with decreased creatinine clearance can, thus, be made on the basis of creatinine clearance.
美罗培南是一种最近研发的碳青霉烯类抗生素，与亚胺培南相似，对革兰氏阳性菌和革兰氏阴性菌均有广泛的抗菌活性。与亚胺培南相比，美罗培南对脱氢肽酶I（DHP-I）的水解作用相对稳定，因此无需与DHP-I抑制剂（如西司他丁）联合使用。此外，美罗培南的肾毒性和神经毒性可能比亚胺培南小。静脉注射1g标准剂量后，血浆美罗培南浓度达到峰值（Cmax）约为30mg/L。消除半衰期（t1/2）约为1小时，血浆浓度-时间曲线下面积与剂量呈线性相关增加。分布容积为21L，表明主要分布在细胞外。美罗培南部分分布于脑脊液中。该药物通过代谢和排泄消除。在正常志愿者中，高达70%的药物在尿液中回收，其余部分由该化合物的β-内酰胺环开环形式ICI 213689构成。肾功能不全患者中美罗培南的t1/2延长，且与肌酐清除率密切相关。因此，肌酐清除率降低的患者可根据肌酐清除率进行剂量调整。
