Ion-Channel Antiepileptic Drugs: An Analytical Perspective on the Therapeutic Drug Monitoring (TDM) of Ezogabine, Lacosamide, and Zonisamide

The term seizures includes a wide array of different disorders with variable etiology, which cur-rently represent one of the most important classes of neurological illnesses. As a consequence, many different antiepileptic drugs (AEDs) are currently available, exploiting different activity mechanisms and providing different levels of performance in terms of selectivity, safety, and ef-ficacy. AEDs are currently among the psychoactive drugs most frequently involved in therapeutic drug monitoring (TDM) practices. Thus, the plasma levels of AEDs and their metabolites are monitored and correlated to administered doses, therapeutic efficacy, side effects, and toxic ef-fects. As for any analytical endeavour, the quality of plasma concentration data is only as good as the analytical method allows. In this review, the main techniques and methods are described, suitable for the TDM of three AEDs belonging to the class of ion channel agents: ezogabine (or re-tigabine), lacosamide, and zonisamide. In addition to this analytical overview, data are provid-ed, pertaining to two of the most important use cases for the TDM of antiepileptics: drug–drug interactions and neuroprotection activity studies. This review contains 146 references.