Interaction between meropenem and valproate: Not to overlook

ABSTRACT

Background Valproic acid is commonly used to treat various types of seizures and follows nonlinear pharmacokinetics with a therapeutic range of 50 - 150 microg/ml. Several retrospective studies have reported that concomitant administration of VPA and carbapenem lead to decrease in VPA levels significantly and results in failure of seizure control. Different studies suggest the mechanism of interaction as [i] carbapenem may inhibit the gastrointestinal absorption of VPA [ii] meropenem accelerated the glucuronidation of VPA to VPA glucuronide [VPA-G] and inhibited the hydrolysis of VPA-G back to the VPA thus increasing the clearance of VPA and VPA-G and [iii] due to fast erythrocyte distribution of VPA by carbapenem, VPA levels has been reduced