Pharmacological aspects of antiseizure medications: From basic mechanisms to clinical considerations of drug interactions and use of therapeutic drug monitoring

Abstract

Antiseizure medications (ASMs) are the cornerstone of treatment for patients with epilepsy. Several new ASMs have recently been introduced to the market, making it possible to better tailor the treatment of epilepsy, as well as other indications (psychiatry and pain disorders). For this group of drugs there are numerous pharmacological challenges, and updated knowledge on their pharmacodynamic and pharmacokinetic properties is, therefore, crucial for an optimal treatment outcome. This review focuses on educational approaches to the following learning outcomes as described by the International League Against Epilepsy (ILAE): To demonstrate knowledge of pharmacokinetics and pharmacodynamics, drug interactions with ASMs and with concomitant medications, and appropriate monitoring of ASM serum levels (therapeutic drug monitoring, TDM). Basic principles in pharmacology, pharmacokinetic variability, and clinically relevant approaches to manage drug interactions are discussed. Furthermore, recent improvements in analytical technology and sampling are described. Future directions point to the combined implementation of TDM with genetic panels for proper diagnosis, pharmacogenetic tests where relevant, and the use of biochemical markers that will all contribute to personalized treatment. These approaches are clinically relevant for an optimal treatment outcome with ASMs in various patient groups.

Pharmacokinetic Variability of Sulthiame: The Impact of Age, Drug–Drug Interactions, and Biochemical Markers of Toxicity in Patients with Epilepsy

“…28,30 This approach is also important with the present drug, which is mainly used for children, for whom physiological changes affect the pharmacokinetics of drugs, leading to increased clearance in children younger than 6 years. 15,31 May et al 6 also found a need for higher dose/kg weight in younger patients ( younger than 14 years) and that most patients use doses <600 mg/d, as in the present study, in which most patients used <400 mg/d. This age-related finding in C/D ratios suggests the usefulness of regular sulthiame measurement to adjust the dosage for variability in pharmacokinetics.…”

“…To elucidate the possible impact of ASM comedication on sulthiame pharmacokinetics, patients were divided into different categories based on coprescribed ASMs, as in previous studies: strong enzyme inducers (carbamazepine, phenobarbital, primidone, and phenytoin), weak enzyme inducers (oxcarbazepine and eslicarbazepine), valproate as a potential enzyme inducer or inhibitor, and clobazam as a possible enzyme inducer. 15,18–22 None of the included patients were instructed to use any other types of drugs with known inducing or inhibiting properties of CYP enzymes. Comedication with ASMs and other drugs considered neutral served as the comparator group, and these patients could not use drugs from other categories.…”

Therapeutic Drug Monitoring (TDM) Implementation in Public Hospitals in Greece in 2003 and 2021: A Comparative Analysis of TDM Evolution over the Years

“…TDM is applied to a wide range of drugs administered in various pathological conditions, such as immunosuppressive drugs used in transplantation or for the treatment of inflammatory bowel disease and autoimmune hepatitis [ 21 ], antifungal agents [ 22 ], antibiotics administered in critically ill patients [ 9 ] or in bacterial infections [ 23 ], antiepileptics [ 24 ], and anticancer drugs [ 4 ]. The main categories of drugs measured in 2003 and 2021 in Greece were antiepileptics, psychiatric drugs, analgesics, immunosuppressants, and antibiotics.…”

Tuning Sodium Channel Blockers to the Near-Atomic Level

“…Others, for example, cannabidiol and cenobamate, have been shown to have additional mechanisms of anticonvulsant action. 2 Generally, “traditional” sodium channel blockers have similar efficacy in controlling focal seizures with some being additionally used for treating generalized epilepsies. 1 The scope of activity has not been fully established for the newer sodium blockers, but their adverse effect profiles might differ from those of older drugs (eg, with regard to sleepiness 3 or induction of drug-metabolizing enzymes).…”