Abstract
The term seizures includes a wide array of different disorders with variable etiology, which currently 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 efficacy. 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 effects. 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 retigabine), lacosamide, and zonisamide. In addition to this analytical overview, data are provided, 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.
Highlights
Epilepsy, and more generally seizures, are one of the most widespread and incapacitating neurologic disorders
The rates of success of antiepileptic treatment can be considerably lower in low-middle income countries (LMIC) than in other parts of the world [4]: lower access to affordable or free public health structures, lower access to cheap medicines, and in some cases even prejudices and open discrimination toward the patients themselves can produce these effects [5], which result in higher disease severity and lethality
We addressed in a previous review the main therapeutic drug monitoring (TDM) characteristics of the following antiepileptic drugs (AEDs): carbamazepine, oxcarbazepine, lamotrigine, phenytoin, ethosuximide, gabapentin, vigabatrin, topiramate, levetiracetam, and valproic acid [20]
Summary
More generally seizures, are one of the most widespread and incapacitating neurologic disorders. Many patients receive a constant monitoring of their AED levels, especially at the beginning of the treatment, to ascertain that correct concentrations are reached without undue risks of overdose and toxic phenomena [13] This practice is commonly named therapeutic drug monitoring (TDM) and is currently being increasingly used to optimize and personalize pharmacological therapy, in particular in the treatment of central nervous system (CNS) disorders [14,15,16,17,18]. We addressed in a previous review the main TDM characteristics of the following AEDs: carbamazepine, oxcarbazepine, lamotrigine, phenytoin, ethosuximide, gabapentin, vigabatrin, topiramate, levetiracetam, and valproic acid [20] In this mini-review, information will be reported on the three other most significant AEDs that interact with ion channels; i.e., ezogabine (or retigabine, EZG), lacosamide (LCS), and zonisamide (ZNS). Some brief notes on possible neuroprotective effects are included, since neuroprotection is one more field where TDM can be eminently useful
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