Bioequivalence in development of antiepileptic drugs

Bioequivalence is an important component of the development of AEDs. Development of new formulations after the original testing of any drug requires demonstration that the compounds are therapeutically equivalent and additional efficacy studies may not be required. Extended-release formulations may reduce toxicity with a lower maximum blood concentration (Cmax) and improve efficacy with a higher minimum blood concentration (Cmin). Obtaining an equivalent area under the curve (AUC) while slowing the gastrointestinal transit and avoiding food effects and dose dumping among a population with epilepsy with individual variability requires extensive engineering of the formulation. The development of extended release divalproex (Depakote® ER) is used as an example of the challenges of this phase of drug development. Other routes of administration discussed are rectal preparations, nasal formulations, and intravenous infusions. These newer formulations may offer better patient care and more efficient development.