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

To investigate the mechanism for the enhanced glucuronidation of valproic a cid (VPA) by panipenem (PAPM), a carbapenem antibiotic, in rat liver, we ca rried 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 t oward VPA both in vivo and in vitro. On the other hand, in vivo treatment w ith 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 proportio nally 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.