Extended release formulations of anticonvulsant medications clinical pharmacokinetics and therapeutic advantages

Abstract

Epilepsy is a chronic disorder that requires adherence to long term anticonvulsant drug therapy for successful outcomes. Most established anticonvulsants must be taken several times a day because of short half-lives and narrow therapeutic indices. Extended release (ER) formulations of some anticonvulsants have been developed to reduce dose frequency and to maintain constant plasma drug concentrations, and to reduce adverse effects. For a drug to be a suitable candidate for ER formulation it must possess the following characteristics: a short half-life, no first-pass metabolism, a narrow therapeutic index, and efficient absorption throughout the gastrointestinal tract. Of the currently available anticonvulsants, carbamazepine and valproic acid (sodium valproate) are the most suitable candidates for ER formulation. Several carbamazepine ER formulations have been developed. These formulations include Carbatrol®, Tegretol-XR®, Tegretol Retard®, Neurotol Slow®, Trimonil Retard® and Teril CR®, among others. Valproic acid ER formulations have also been developed. Although there are currently no ER formulations of valproic acid marketed in the US, several are available in Europe including Epilim Chrono® and Depakine Chrono®. The Depakote Sprinkle® formulation is also available in some European countries. Of the newer anticonvulsants tiagabine is the most likely candidate for future ER formulation. ER formulations offer the advantage of better patient compliance due to decreased frequency of administration and adverse effects. Also, less fluctuation in plasma concentrations makes monitoring of drug concentrations more viable. These advantages should lead to better seizure control and improve quality of life for the patient.