Pharmacokinetic properties of current antiepileptic drugs: what improvements are needed?

Abstract

The pharmacokinetics of antiepileptic drugs (AEDs) largely determine their ability to achieve and maintain concentrations that maximize their efficacy and safety. The term "pharmacokinetics" encompasses the quantitative assessment of changes of drug concentrations over time as a function of absorption, distribution, and elimination. Interaction among AEDs, and between AEDs and other classes of drugs, can result in undesirable drug levels. The pharmacokinetic properties of AEDs considered to be clinically most relevant include complete or constant bioavailability, availability of a parenteral formulation, elimination half-life or preparation suitable for once- or twice-daily dosing, linear elimination kinetics, no autoinduction of enzymatic biotransformation, and lack of pharmacokinetic interactions with other drugs. Both established AEDs (carbamazepine, phenytoin, valproate, phenobarbital, and primidone) and newer AEDs (oxcarbazepine, felbamate, gabapentin, lamotrigine, topiramate, tiagabine) are evaluated in terms of these properties. None of the currently marketed AEDs combines all of these desirable pharmacokinetic characteristics. However some of the newer AEDs have more favorable pharmacokinetic profiles. The main improvements needed are limited or no pharmacokinetic interactions, preparations suitable for once- or twice-daily administration, and availability of parenteral formulations.