The effect of carbapenem antibiotics on plasma concentrations of valproic acid

The Annals of Pharmacotherapy
Erin E Mancl, Barry E Gidal

Abstract

To critically evaluate the mechanisms of the interaction between valproic acid and carbapenem antibiotics. A PubMed search (January 1971-June 2009) was performed to identify literature on the interaction between valproic acid and carbapenem antibiotics. Additional references were identified through review of bibliographies of identified articles. Data on the mechanisms of the interaction between valproic acid and carbapenem antibiotics were extracted from identified references that were published in English. Valproic acid plasma concentrations fall markedly during concomitant administration with carbapenem antibiotics due to a combination of absorption, distribution, and metabolism mechanisms. Carbapenems appear to inhibit the intestinal transporter of valproic acid, thereby reducing absorption of orally administered valproic acid. In vivo experiments in rats demonstrate a 57% reduction in absorption of orally administered valproic acid in the presence of imipenem. Follow-up studies in Caco-2 cells suggest that the inhibition probably occurs at the basolateral membrane. In addition, enterohepatic recycling of valproic acid may be diminished due to carbapenem activity against gut flora producing beta-glucuronidase. When rabbits ...Continue Reading

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