Relevance of CYP2C9 Function in Valproate Therapy

Background: Genetic polymorphisms of drug metabolizing enzymes can substantially modify the pharmacokinet-ics of a drug and eventually its efficacy or toxicity; however, inferring a patient’s drug metabolizing capacity merely from his or her genotype can lead to false prediction. Non-genetic host factors (age, sex, disease states) and environmental factors (nutrition, co-medication) can transiently alter the enzyme expression and activities resulting in genotype-phenotype mis-match. Although valproic acid is a well-tolerated anticonvulsant, pediatric patients are particularly vulnerable to valproate in-jury that can be partly attributed to the age-related differences in metabolic pathways.