Antiepileptic drug pharmacokinetics and interactions: Impact on treatment of epilepsy

An understanding of epilepsy therapy's pharmacokinetic and drug interaction principles-combined with knowledge of antiepileptic drug (AED) clinical pharmacology-allows more effective use of these drugs. The most desirable pharmacokinetic characteristic is a linear relationship between dose and steady-state concentration, as this determines the ease or difficulty in determining the appropriate dose. Drug-drug interactions affecting AED metabolism are common, clinically important, and, until recently, often unpredictable. Advances in molecular biology have identified specific enzymes responsible for AED metabolism and interactions. Clinicians now can identify potential interactions and avoid or manage them by adjusting drug dosage. Most newer AEDs follow or approximate linear pharmacokinetics, are absorbed extensively and consistently, are not significantly bound to plasma proteins, do not form active metabolites, and have few, if any, drug interactions. In cases where interactions occur between newer AEDs and other drugs, knowledge of these interactions reduces the likelihood of serious adverse events. The pharmacokinetics of the newer AEDs simplify drug dosing and monitoring and should lead to improved patient care.