Chapter 9 Therapeutic drug monitoring of antiepileptic drugs

Abstract

The aim of the present chapter is to discuss therapeutic drug monitoring (TDM) of the established and newer antiepileptic drugs (AEDs), based on their pharmacokinetic properties and mode of action. Analytical methods for the determination of the serum concentrations of these drugs are also briefly described. Due to the nature of epilepsy, it remains problematic to monitor AED treatment by direct observations of clinical response in the individual patient. A reasonably good correlation between serum drug concentration and clinical effect together with large inter-individual differences in the rate of drug clearance, are factors that together with the need to identify toxicity, test compliance and elucidate possible clinical interactions would make TDM desirable. Few studies have been designed primarily to study the serum concentration-effect relationships. As TDM is not widely practiced for the newer AEDs there are no generally accepted target ranges for any of these drugs, and for most a wide range in serum concentration is associated with clinical efficacy. Also, a considerable overlap in drug concentrations related to toxicity and non-response is reported. Further systematic studies designed specifically to evaluate concentration-effect relationships of the new AEDs are urgently needed. Measurements of some of the drugs are undoubtedly of help with individualisation of treatment in selected cases in a particular clinical setting. There are large differences between individuals in response to particular drugs and drug concentrations, thus the primary role of TDM for both the established and newer AEDs is to identify the individual optimum concentration and thus establish a reference value in that patient.