Single-dose pharmacokinetics and anticonvulsant efficacy of primidone in mice.

The pharmacokinetics and efficacy of the anticonvulsant primidone (PRM) and its active metabolites, phenobarbital (PB) and phenylethylmalonamide (PEMA), were studied after single-dose administration in mice. The half-life of PB is twice that of PRM and PEMA. The plasma/brain ratios provide evidence of poor penetration of PRM into brain. The results support our findings of negligible or absent PRM concentrations in the brains of patients on primidone therapy who were undergoing surgery for intractable epilepsy. The anticonvulsant properties of PRM, PB, and PEMA against maximal electroshock in mice were also studied with the use of the metabolic inhibitor SKF 525A. The half-life, potency, peak anticonvulsant effect, and effective dose curves of these compounds indicate that the anticonvulsant effect of short-term oral PRM administration in mice is from derived PB.