Pharmacokinetic properties of current antiepileptic drugs - What improvements are needed?

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 asses sment of changes of drug concentrations over time as a function of absorpti on, distribution, and elimination. Interaction among AEDs, and between AEDs and other classes of drugs, can result in undesirable drug levels. The pha rmacokinetic properties of AEDs considered to be clinically most relevant i nclude complete or constant bioavailability, availability of a parenteral f ormulation, elimination half-life or preparation suitable for once- or twic e-daily dosing, linear elimination kinetics, no autoinduction of enzymatic biotransformation, and lack of pharmacokinetic interactions with other drug s. Both established AEDs (carbamazepine, phenytoin, valproate, phenobarbita l, and primidone) and newer AEDs (oxcarbazepine, felbamate, gabapentin, lam otrigine, topiramate, tiagabine) are evaluated in terms of these properties . None of the currently marketed AEDs combines all of these desirable pharm acokinetic characteristics. However some of the newer AEDs have more favora ble pharmacokinetic profiles. The main improvements needed are limited or n o pharmacokinetic interactions, preparations suitable for once- or twice-da ily administration, and availability of parenteral formulations.