帕尼培南，一种碳青霉烯类抗生素，可提高大鼠肝脏中尿苷二磷酸葡萄糖醛酸的水平。

Panipenum, a carbapenem antibiotic, increases the level of hepatic UDP-glucuronic acid in rats.

作者信息

Yamamura N, Imura-Miyoshi K, Naganuma H

机构信息

Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.

出版信息

Drug Metab Dispos. 2000 Dec;28(12):1484-6.

PMID:11095587

Abstract

To investigate the mechanism for the enhanced glucuronidation of valproic acid (VPA) by panipenem (PAPM), a carbapenem antibiotic, in rat liver, we carried out studies to investigate whether PAPM increases the activity of UDP-glucuronosyltransferase or the level of hepatic UDP-glucuronic acid (UDPGA) in rats. PAPM had no effect on the UDP-glucuronosyltransferase activity toward VPA both in vivo and in vitro. On the other hand, in vivo treatment with PAPM significantly increased the hepatic UDPGA level by about 1.7-fold (control: 434.5 +/- 65.5 nmol/g of liver; PAPM-treated: 755.2 +/- 92.3 nmol/g of liver). The in vitro formation of VPA glucuronide increased proportionally as a function of the UDPGA concentration up to 0.8 mM. Therefore, the increase in the level of hepatic UDPGA by PAPM is likely to be one of the causal factors for enhancing VPA glucuronidation in vivo.

摘要

为研究碳青霉烯类抗生素帕尼培南（PAPM）增强大鼠肝脏中丙戊酸（VPA）葡萄糖醛酸化作用的机制，我们开展了研究，以探究PAPM是否会增加大鼠体内尿苷二磷酸葡萄糖醛酸基转移酶（UDP - 葡萄糖醛酸基转移酶）的活性或肝脏中尿苷二磷酸葡萄糖醛酸（UDPGA）的水平。PAPM在体内和体外对VPA的UDP - 葡萄糖醛酸基转移酶活性均无影响。另一方面，PAPM体内给药显著提高了肝脏UDPGA水平，约为对照组的1.7倍（对照组：434.5±65.5 nmol/g肝脏；PAPM处理组：755.2±92.3 nmol/g肝脏）。在体外，VPA葡萄糖醛酸苷的形成随UDPGA浓度增加而呈比例增加，直至0.8 mM。因此，PAPM导致肝脏UDPGA水平升高可能是其增强体内VPA葡萄糖醛酸化作用的原因之一。