Identification of valproic acid glucuronide hydrolase as a key enzyme for the interaction of valproic acid with carbapenem antibiotics.

Characterization of inhibitory effect of carbapenem antibiotics on the deconjugation of valproic acid glucuronide.

Serum concentrations of valproic acid (VPA) are markedly decreased by coadministration of carbapenem antibiotics (CBPMs). Although inhibition of deconjugation of VPA-glucuronide (VPA-G) to VPA by CBPMs has been proposed as one of the mechanisms to account for this drug-drug interaction, little information is available on the mode of inhibition. In the present study, we characterized the enzyme ...

Mechanism of Drug Interaction between Valproic Acid and Carbapenem Antibiotics via Acylpeptide Hydrolase

Valproic Acid-Induced Time Dependent Craniofacial Defects in Wistar Rat Fetuse

Purpose: we previously reported that maternal valproic acid (VA) administration during rat pregnancy produced CNS defect ranely, syringomyelia. Furthermore, it seems that administration of valproic acid during critical period of pregnancy may affect on development of other embryonic skeletal portion such as craniofacial region. The goal of our study was to determine whether there is a relations...

Panipenem, a carbapenem antibiotic, enhances the glucuronidation of intravenously administered valproic acid in rats.

Previously, a significant decrease in the trough plasma-concentration of valproic acid (VPA) owing to the concomitant administration of panipenem (PAPM)/betamipron, a carbapenem antibiotic, in epileptic patients was reported. To determine the site and mechanism of the drug interaction between VPA and PAPM, we performed in vivo and in vitro experiments using rats. A 30 mg/kg bolus dose of VPA wa...

Mechanism of the drug interaction between valproic acid and carbapenem antibiotics in monkeys and rats.

The Ministry of Health and Welfare, Japan banned coadministration of carbapenems, such as panipenem/betamipron (PAPM), meropenem (MEPM), and valproic acid (VPA) because clinical reports have indicated that the coadministration caused seizures in epileptic patients due to lowered plasma levels of VPA. In this study, we have clarified the mechanism of the drug-drug interaction using PAPM, MEPM, a...