Therapeutic monitoring of the new antiepileptic drugs

Objective: To discuss the potential value of therapeutic drug monitoring (TDM) of the new antiepileptic drugs gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide. Methods: A review of studies of the relationship between plasma concentrations and effects of new antiepileptic drugs is provided. Furthermore, the potential value of TDM of these drugs is discussed in relation to their mode of action and their pharmacokinetic properties. The various methods that are available for analysing plasma concentrations of the new antiepileptic drugs are also briefly reviewed. Results. The available information on the relationship between plasma concentrations and effects of the new drugs is scarce. For most drugs, wide ranges in concentrations associated with seizure control are reported, and a considerable overlap with drug levels among nonresponders and also with concentrations associated with toxicity is often noted. However, very few studies have been designed primarily to explore the relationship between drug plasma concentrations and effects. Consequently, there are no generally accepted target ranges for any of the new antiepileptic drugs. Although the available documentation clearly is insufficient, the pharmacological properties of some of the drugs, in particular lamotrigine, zonisamide and, possibly, oxcarbazepine, topiramate and tiagabine, suggest that they may be suitable candidates for TDM. Conclusion: TDM of some of the new antiepileptic drugs may be of value in selected cases, although routine monitoring in general cannot be recommended at this stage. Further systematic studies designed specifically to investigate concentration-effect relationships of the new antiepileptic drugs are urgently needed.