ABSTRACT
Primidone (PRM) was first synthesized by Bogue and Carrington, and its clinical efficacy as an antiepileptic drug was reported in 1952 by Handley and Stewart. The oral absorption of PRM has been studied in patients with epilepsy. The mechanism of action of PRM is a complex issue for two reasons. First, PRM has two active metabolites, phenobarbital (PB) and phenylethylmalonamide and, second, it is difficult to test PRM in the absence of these metabolites. A significant change in the toxicity to serum level ratio of PRM could be demonstrated in patients as early as 6 hours after the first exposure to PRM. Also, a cross-tolerance between PB and PRM leading to reduced acute PRM toxicity after previous exposure to PB has been suggested in patients and could be demonstrated quantitatively in experimental animals. Chronic adverse effects of PRM, which are generally dose related, include sedation, nystagmus, ataxia, vertigo, and decreased libido or impotence.
