The pharmacogenomics of valproic acid.

Valproic acid is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. Adverse effects of valproic acid are rare, but hepatotoxicity is severe in particular in those younger than 2 years old and polytherapy. During valproic acid treatment, it is difficult for prescribers to predict its individual response. Recent advances in the field of pharmacogenomics have indicated variants of candidate genes that affect valproic acid efficacy and safety. In this review, a large number of candidate genes that influence valproic acid pharmacokinetics and pharmacodynamics are discussed, including metabolic enzymes, drug transporters, neurotransmitters and drug targets. Furthermore, pharmacogenomics is an important tool not only in further understanding of interindividual variability but also to assess the therapeutic potential of such variability in drug individualization and therapeutic optimization.