Pharmacokinetic evaluation of sustained release formulations of antiepileptic drugs. Clinical implications.

Epilepsy is a chronic disease that requires long term therapy, and most of the established antiepileptic drugs (the exception is phenobarbital) must be administered several times daily. This results in compliance problems and fluctuations in plasma concentrations which may lead to subtherapeutic and potentially toxic levels. Development of sustained release formulations of the existing antiepileptic agents may improve antiepileptic therapy. At present, only the following 4 major drugs are used for the treatment of epilepsy: phenobarbital, phenytoin, carbamazepine and valproic acid. Of these, only the latter 2 are suitable candidates for sustained release formulations. This review, therefore, focuses on the evaluation and clinical implications of sustained release formulations of valproic acid and carbamazepine.