Shimada J, Kawahara Y
Division of Clinical Pharmacology, St. Marianna University School of Medicine, Kawasaki, Japan.
Drugs Exp Clin Res. 1994;20(6):241-5.
Carbapenems are beta-lactam antibiotics with a broad antibacterial spectrum and a potent bactericidal activity against both aerobic and anaerobic Gram-positive and Gram-negative organisms. They have been widely investigated in the past, and imipenem/cilastatin (IPM/CS), panipenem/betamipron (PAPM/BP), meropenem (MEPM) and biapenem (BIPM) are presently in clinical use or under trial. Of the carbapenems, imipenem is not readily hydrolysed by microbial beta-lactamase but is hydrolysed to open the beta-lactam ring by DHP-I from kidney and other tissues. In order to achieve greater stability to the enzyme and to prolong the action of the carbapenem in vivo, the co-administration of CS with IPM or the attainment of the chemical construction of the 1-beta methylcarbapenem derivatives in the case of MEPM and BIPM have been performed. However, some difference was found in the DHP-I activity with these carbapenems, but there was no significant difference in the pharmacokinetic parameters: AUC, CLtot, t1/2 and MRT except urinary clearance after administration of these compounds to humans. Considering that MRT as the amount of the antibiotics retained in the body is a clinically important parameter, the structural susceptibility of the carbapenems to the decomposition by DHP-I was suggested to have no clinically meaningful correlation with the pharmacokinetics of these compounds.
碳青霉烯类是一类β-内酰胺抗生素，具有广谱抗菌活性，对需氧和厌氧的革兰氏阳性及革兰氏阴性菌均有强大的杀菌作用。过去对其进行了广泛研究，目前亚胺培南/西司他丁（IPM/CS）、帕尼培南/倍他米隆（PAPM/BP）、美罗培南（MEPM）和比阿培南（BIPM）已在临床应用或处于试验阶段。在碳青霉烯类中，亚胺培南不易被微生物β-内酰胺酶水解，但会被肾脏及其他组织中的DHP-I水解开环。为提高对该酶的稳定性并延长碳青霉烯类在体内的作用时间，采取了将西司他丁与亚胺培南联合应用，或在美罗培南和比阿培南的情况下构建1-β甲基碳青霉烯衍生物的化学结构等方法。然而，这些碳青霉烯类在DHP-I活性方面存在一些差异，但在药代动力学参数（AUC、CLtot、t1/2和MRT）方面没有显著差异，只是在给人体使用这些化合物后尿清除率有所不同。鉴于MRT作为抗生素在体内留存量是一个重要的临床参数，提示碳青霉烯类对DHP-I分解的结构敏感性与这些化合物的药代动力学没有临床意义上的相关性。
