Interaction between valproic acid and carbapenems: decreased plasma concentration of valproic acid and liver injury

BACKGROUND: Several case reports and retrospective studies have indicated that carbapenems decrease the plasma concentration of valproic acid (VPA). This retrospective study examines the effect of carbapenems on VPA levels, and explores whether the drug-drug interaction can influence the liver function of patients. METHODS: The data of 141 patients were collected from the Department of Neurosurgery at Shanxi Bethune Hospital from January 2018 to December 2019. We compared the VPA levels between the VPA monotherapy group and VPA + carbapenem group to evaluate the influence of carbapenem antibiotics on the plasma concentration of VPA. We also compared the liver injury rate of the VPA monotherapy group, VPA + meropenem group, and VPA + imipenem group to evaluate the influence of concomitant use of VPA with carbapenem antibiotics on liver function. RESULTS: The VPA serum concentration in the VPA + meropenem group was 22.32±21.77 µg/mL, which was markedly lower than that in the VPA monotherapy group (i.e., without carbapenems) (65.17±21.49 µg/mL) (P<0.01). The rate of liver injury was significantly different between the VPA monotherapy, VPA + meropenem, and VPA + imipenem groups (χ2=30.13, P<0.01). Further comparisons showed that the liver injury rate of the VPA + meropenem group (35.42%) was higher than that of the VPA + imipenem (3.7%) and VPA monotherapy (1.52%) groups (P<0.01). Although no significant differences in liver injury rate were observed between the VPA + imipenem (3.7%) and VPA monotherapy (1.52%) groups, the alanine aminotransferase (ALT) value of the VPA + imipenem group after co-administration (65.22±48.01 U/L) was notably higher than before (40.48±24.97 U/L) (P<0.01). CONCLUSIONS: In this study, the interaction between VPA and carbapenems resulted in decreased plasma concentrations of VPA as well as possible liver injury. Clinicians should be aware of this potential interaction, and closely monitor VPA concentrations and liver function. Different carbapenems combined with VPA showed different effects on both VPA concentration and liver function, indicating that the mechanisms of these two effects might be related.