Interaction between Cytochrome P450 Isozymes and Antiseizure Medications: A Literature Review

Antiseizure medications (ASMs) are frequently utilized either as ongoing supplementary treatment or as the primary therapy for epilepsy. Different ASMs either inhibit of induce isoenzymes of CYP450 system, potentially altering the pharmacokinetic characteristics of various medications, including in polytherapy of ASMs. This study investigate the interaction between CYP450 and ASMs, with emphasis on pharmacokinetic interactions. This literature study included publications from the last 5 years (2018-2023) that are relevant to the topic and important publications retrieved and reviewed from the PubMed, ResearchGate, and Google Scholar databases by using a combination of main keywords "antiseizure medications", "cytochrome P450", "pharmacokinetics", "metabolism" and other relevant keywords. It was found that due to the role of CYP450 enzymes in metabolizing most therapeutic drugs, individuals using ASMs that induce these enzymes may metabolize a diverse array of concurrently administered medications more rapidly, potentially leading to an increase in dosage requirements. Phenytoin, primidone, phenobarbital and carbamazepine enhance the function of various cytochrome P450 (CYP) enzymes, such as CYP2C9, CYP1A2, CYP3A4 and CYP2C19. On the other hand, inhibition of these enzymes could elevate the plasma level of drugs that are metabolized via those enzymes. Valproic acid and oxcarbazepine are the examples of CYP450 inhibitors. The majority of significant interactions involving ASMs in clinical contexts arise from either the stimulation or suppression of CYP450 drug-metabolizing enzymes. These interactions can lead to alterations in the pharmacokinetic characteristics of various medications. Typically, adjustments to the dosage of the affected AED are necessary. Additional research and investigations are necessary regarding possible interaction between CYP450 and newer ASMs to determine the possible outcome due to these interactions.