Chapter 10 - Therapeutic monitoring of antiepileptic drugs

Abstract

Abstract The aim of the present chapter is to discuss therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs), based on their pharmacokinetic properties in order to optimize the therapy to the individual patient. 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 interindividual 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. Several of the older drugs like phenytoin and valproate have a narrow spectrum of serum concentrations in which efficacy and not toxicity is likely to occur. For newer AEDs, there is a wide range in serum concentration associated with clinical efficacy for most drugs. Also, a considerable overlap in drug concentrations related to toxicity and nonresponse is reported. Further systematic studies designed specifically to evaluate concentration–effect relationships of the new AEDs are urgently needed. Reference ranges are established for all drugs. Implementation of serum concentration measurements is a valuable tool for individualisation of treatment based on a clinical evaluation. 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 an individual therapeutic concentration in that patient to follow over time to improve quality assurance and patient safety.