Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
Institute of Hospital Pharmacy, Central South University, Changsha, China.
J Hum Genet. 2017 Dec;62(12):1009-1014. doi: 10.1038/jhg.2017.91. Epub 2017 Sep 7.
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.
丙戊酸是一种抗惊厥和情绪稳定药物，主要用于治疗癫痫和双相情感障碍。丙戊酸的不良反应罕见，但肝毒性尤其严重，尤其是在 2 岁以下和联合用药的情况下。在丙戊酸治疗期间，医生难以预测其个体反应。药物基因组学领域的最新进展表明，候选基因的变异会影响丙戊酸的疗效和安全性。在这篇综述中，讨论了大量影响丙戊酸药代动力学和药效学的候选基因，包括代谢酶、药物转运体、神经递质和药物靶点。此外，药物基因组学不仅是进一步了解个体间变异性的重要工具，也是评估药物个体化和治疗优化中这种变异性治疗潜力的重要工具。
