丙戊酸药物基因组学的研究进展

发布时间：2018-05-01 18:51

本文选题：丙戊酸 + 药物基因组学　；参考：《中国药房》2017年26期

【摘要】：目的:了解丙戊酸(VPA)药物基因组学的研究进展,以期为其临床个体化用药提供参考。方法:查阅近年来国内外相关文献,就VPA的代谢、转运和效应通路相关基因多态性对其药效影响的研究进行归纳和总结。结果:VPA的药效受药物代谢相关基因、转运基因和效应通路相关基因的影响。药物代谢酶中葡糖醛酸的代谢途径中的尿苷二磷酸葡糖醛酸基转移酶(UGT)1A6和UGT2B7基因多态性对VPA药效学的影响尚存在争议,线粒体内的β-氧化途径和细胞色素P_(450)(CYP)(主要为CYP2C9、CYP2C19、CYP2A6和CYP2B6)介导的氧化途径是引起患者给予VPA后发生不良反应的主要原因。转运基因和效应通路相关基因对VPA药效的影响研究具有十分重要的指导意义,但尚缺乏临床对照试验和临床终点数据为VPA相关基因组学指导个体化给药提供可靠依据。结论:随着VPA药物基因组学的不断发展和完善,其更多的功能基因和特性的明确将推动VPA个体化给药的实现,提高患者用药的安全性和有效性。
[Abstract]:Objective: to investigate the progress of pharmacogenomics of valproic acid (VPA) in order to provide reference for clinical individualized drug use. Methods: to review the related literatures in recent years and summarize the effects of VPA metabolism, transport and effect pathway gene polymorphism on its pharmacodynamics. Results the drug efficacy of VPA was affected by the genes related to drug metabolism, translocation and effect pathway. The effects of UGT1A6 and UGT2B7 gene polymorphisms in the glucuronic acid metabolic pathway of drug metabolizing enzymes on the pharmacodynamics of VPA are still controversial. The 尾 -oxidation pathway in mitochondria and cytochrome Pill 450 (mainly CYP2C9, CYP2C19CYP2A6 and CYP2B6) mediated oxidation pathway are the main causes of adverse reactions after VPA. The study on the effects of transporter genes and effect-pathway genes on the pharmacodynamics of VPA is of great significance, but the clinical controlled trials and clinical endpoint data are lacking to provide reliable basis for the guidance of VPA genomics in individualized drug delivery. Conclusion: with the development and improvement of VPA pharmacogenomics, more functional genes and characteristics will promote the realization of individual administration of VPA, and improve the safety and efficacy of drug use in patients.
【作者单位】：昆明市第一人民医院药学部;大理大学药学与化学学院;
【分类号】：R96

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