Important pharmacokinetic properties of antiepileptic drugs.

Abstract

The choice of an antiepileptic drug (AED) is guided primarily by efficacy and safety criteria. However, the pharmacokinetic properties of an AED determine its ease of use, i.e., its ability to predictably produce and maintain optimal plasma concentrations. Desirable and clinically important pharmacokinetic properties of an AED include complete or constant bioavailability, slow enteral absorption or availability of a sustained-release formulation, availability of a parenteral formulation for acute treatment, rapid penetration into the brain, a single-compartment volume of distribution, low and nonsaturable protein binding, and linear elimination kinetics, with an elimination half-life of about 24 h. The absence of autoinduction of enzymatic biotransformation, active metabolites, and pharmacokinetic drug interactions is also important. In clinical practice, the most undesirable pharmacokinetic properties are lack of a parenteral formulation, short elimination half-life, nonlinear elimination kinetics, autoinduction of enzymatic biotransformation, and interaction with other drugs. No AED is presently marketed or under development that meets all of the desirable criteria. Some of the newer AEDs, although not "ideal" agents, have pharmacokinetic profiles that are not shared by their predecessors, including elimination exclusively by the kidney, absence of drug interactions, and dose-related bioavailability.