Extended release formulations of anticonvulsant medications - Clinical pharmacokinetics and therapeutic advantages

Epilepsy is a chronic disorder that requires adherence to long term anticon vulsant drug therapy for successful outcomes. Most established anticonvulsa nts must be taken several times a day because of short half-lives and narro w therapeutic indices. Extended release (ER) formulations of some anticonvu lsants have been developed to reduce dose frequency and to maintain constan t plasma drug concentrations, and to reduce adverse effects. For a drug to be a suitable candidate for ER formulation it must possess th e following characteristics: a short half-life, no first-pass metabolism, a narrow therapeutic index, and efficient absorption throughout the gastroin testinal tract. Of the currently available anticonvulsants, carbamazepine a nd valproic acid (sodium valproate) are the most suitable candidates for ER formulation. Several carbamazepine ER formulations have been developed. These formulatio ns include Carbatrol(R), Tegretol-XR(R), Tegretol Retard(R), Neurotol Slow( R), Trimonil Retard(R) and Teril CR(R), among others. Valproic acid ER form ulations have also been developed. Although there are currently no ER formu lations of valproic acid marketed in the US, several are available in Europ e including Epilim Chrono(R) and Depakine Chrono(R). The Depakote Sprinkle( R) formulation is also available in some European countries. Of the newer anticonvulsants tiagabine is the most likely candidate for fut ure ER formulation. ER formulations offer the advantage of better patient compliance due to dec reased frequency of administration and adverse effects. Also, less fluctuat ion in plasma concentrations makes monitoring of drug concentrations more v iable. These advantages should lead to better seizure control and improve q uality of life for the patient.