Pharmacological interactions of mesuximide with phenobarbital and phenytoin in hospitalized epileptic patients.

In order to study the pharmacological interactions of the anticonvulsant drugs mesuximide (MSM), phenobarbital (PB), and phenytoin (PHT), serum concentrations of N-desmethyl-mesuximide (N-DESM-MSM, the main metabolite of MSM), PB, and PHT were determined in 94 hospitalized patients suffering from petit mal epilepsy. When MSM was administered to patients on stable PB or primidone therapy, the mean concentrations of PB increased by statistically significant amounts of 38 and 40%, respectively. Similarly, the additional administration of MSM caused the mean concentration of PHT to rise by 78%. The data also indicate that patients with PB and/or PHT comedication have higher N-DESM-MSM serum concentrations than patients without comedication. The pharmacological reasons for these interactions are discussed. These studies demonstrate that the disturbing side effects of MSM are often due to the co-medication. A carefully planned therapeutical dose procedure with regular serum level determinations is proposed to avoid or at least reduce the adverse effects of MSM.