Study of the hepatic metabolism of primidone by improved methodology

The metabolism of the anticonvulsant drug primidone (PRM) was studied in the isolated perfused rat liver by a radiotracer methodology that permits nearly quantitative accounting of the dose as drug and identified metabolites. 14C-PRM and its metabolites were separated by thin-layer chromotography and quantitated by liquid-scintillation counting PRM was extensively converted to known active metabolites: phenobarbital (PB), 15%, and phenylethylmalonamide, 80%, in control livers during 120 minutes. Pretreatment of rats with PB greatly accelerated the rate of PRM metabolism, pretreatment with PRM only moderately so. There was no differential induction of the two metabolism pathways. Addition of phenylethylmalonamide to the perfusate reduced the rate of PRM metabolism but addition of PB did not. It is concluded that conversion of PRM to its active metabolites may be simultaneously influenced by the processes of metabolite induction (PB) and metabolite inhibition (phenylethylmalonamide).