抗癫痫药的群体药代动力学与CYP450 基因多态性的研究进展

摘要/Abstract

摘要： 抗癫痫药代谢的个体差异较大, 需要个体化用药。群体药代动力学的研究是设计个体化治疗方案的有效方法。国内外对新老抗癫痫药的群体药代动力学进行了广泛研究, 分析了一般生物学特征对药物代谢的影响。CYP450 基因多态性是影响抗癫痫药物代谢的主要遗传因素, 是个体差异的重要原因。目前, 已有研究将CYP450 基因多态性的因素引入群体药代动力学的模型, 将其对抗癫痫药物代谢的影响进行了量化, 并且, 可以依据不同的基因型选择不同的初始剂量, 促进个体化治疗, 取得了新的进展。但是, 有项研究提示基因多态性对群体药代动力学( PPK) 参数的影响没有统计学意义。因此,目前的结论尚不完全一致, 需要进一步研究。

关键词: 群体药代动力学, 抗癫痫药, CYP450, 基因多态性

Abstract: Antiepileptic drugs ( AEDs) should be used with individualized dsage regimens since they are metabolized by marked variability.It is an effective way to design individualized dosage regimens with population pharmacokinetic ( PPK) researching.There are lots of researches on PPK for antiepileptic drugs in the world, and many demographic features but genetic factors are analyzed in PPK models.CYP450 gene polymorphisms are important factors for interindividual variability.The latest advance of study for PPK is to analyze the effect on AEDs due to CYP450 gene polymorphisms, and to choose different initial doses according to gene polymorphisms.It will be valuable to facilitate individualized dosage regimen.However, one study indicates that the presently evaluated variant alleles in the CYP2C8, CYP3A4, CYP3A5 and ABCB1 genes did not explain the substantial interindividual variability in paclitaxel pharmacokinetics.Therefore,more deeply research should be done.

Key words: population pharmacokinetics, antiepileptic drugs, CYP450, gene polymorphisms

中图分类号:

R969.1

姜德春, 白向荣, 王育琴, 李林. 抗癫痫药的群体药代动力学与CYP450 基因多态性的研究进展[J]. 中国临床药理学与治疗学, 2006, 11(11): 1207-1212.

JIANG De-chun, BAI Xiang-rong, WANG Yu-qin, LI Lin. Advances in studies on population pharmacokinetics of antiepileptic drugs and CYP450 gene polymorphisms[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(11): 1207-1212.

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