What is the suspected mechanism of carbapenem-induced reduction in valproic acid serum concentrations?
Acylpeptide hydrolase inhibition. Valproic acid is conjugated with glucuronic acid in the liver and excreted in bile. Acylpeptide hydrolase in the gastrointestinal tract removes glucuronic acid causing reabsorption of valproic acid and longer serum half-life. Carbapenems appear to cause irreversible inhibition of acylpeptide hydrolase which prevents valproic acid reabsorption.
Dreucean D, et al. Use of meropenem to treat valproic acid overdose. Am J Emerg Med 2019;37(11):2120.e5-2120.e7. doi: 10.1016/j.ajem.2019.158426.