A Systematic Review of the Impact of Garlic Constituents on Cytochrome P450–Mediated Phenytoin Pharmacokinetics, Pharmacodynamics, and Therapeutic Outcomes
Phenytoin, an antiepileptic drug known for its complex pharmacokinetics and narrow therapeutic range, may interact with garlic (Allium sativum). Garlic affects CYP450 enzymes and P-glycoprotein, potentially affecting the metabolism, transport, efficacy, and toxicity of phenytoin. This systematic review aims to assess the existing evidence regarding pharmacokinetic and pharmacodynamic interactions between garlic and phenytoin. A thorough literature review was performed utilizing PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar. Relevant research was examined and integrated in accordance with PRISMA criteria to present a summary of existing knowledge. Data from in vitro studies, animal models, and restricted clinical reports were examined to evaluate the influence of garlic on phenytoin absorption, metabolism, plasma levels, and treatment effectiveness. Mechanistic findings, heterogeneity in garlic formulations, and therapeutic implications for epilepsy management were also examined. In vitro and pharmacokinetic studies indicate that garlic may either increase or inhibit the metabolism of phenytoin. However, conclusive determinations cannot be drawn owing to the lack of substantial human research. Available findings suggest a potential interaction between garlic and phenytoin involving CYP450 enzymes and P-glycoprotein. However, inconsistent experimental outcomes and inadequate clinical evidence prevent definitive conclusions. The variability of garlic formulations hampers interpretation, highlighting the necessity for careful clinical application and rigorously planned human trials in epilepsy management. Clinicians should exercise vigilance and systematically inquire about garlic consumption in patients undergoing phenytoin therapy. Controlled clinical trials are necessary to validate these findings and ascertain the safety of garlic in combination with phenytoin.