CYP2A6*4基因多态性对右美托咪定药动学的影响

doi:10.12092/j.issn.1009-2501.2018.12.009

摘要/Abstract

摘要：

目的: 在CYP2A6*4突变频率高的中国人中测定CYP2A6*4等位基因对右美托咪定药代动力学的影响，为临床提供参考。方法: 31名手术患者通过静脉泵接受0.5 μg/kg右美托咪定后，抽取多个时间点的血样，测定血药浓度以及CYP2A6*4的多态性，并进行统计分析。结果: 9名患者为*1/*4或*4/*4，22名患者为*1/*1。主要药代动力学参数如下，曲线下面积（AUC）为（1 396.19±332.47）h·ng·L^-1，峰值血药浓度（C _max）为（495.50±104.90）ng/L，分布容积（V）为（0.68±0.20）L/kg，清除率（CL）为（0.38±0.11）L·h ^-1·kg^-1，分布半衰期（t _1/2α）为（0.05±0.01）h，消除半衰期（t _1/2β）为（2.53±0.04）h。在CYP2A6*1/*1，*1/*4和*4/*4患者中未发现显著的药代动力学差异。结论: 中国患者使用右美托咪定后，t _1/2β与公布的一致，但t _1/2α，V和CL较低。在制定右美托咪定的精准治疗方案时，可不予考虑CYP2A6*4突变。

关键词: 右美托咪定, CYP2A6, 药动学, 基因多态性

Abstract:

AIM: To determine the dexmedetomidine pharmacokinetics of CYP2A6*4 allele in Chinese patients with high mutation frequency of CYP2A6*4 in order to provide clinical references. METHODS: Thirty-one surgery patients received 0.5 μg/kg dexmedetomidine via intravenous pump. Their plasma concentrations at multiple time-points and polymorphism of CYP2A6*4 were determined and statistically analyzed.RESULTS:Nine patients were *1/*4 or *4/*4 , and 22 patients were *1/*1. The main pharmacokinetic parameters were area under curve (AUC) （1 396.19±332.47）h·ng·L-1, peak blood concentration (Cmax) （495.50±104.90）ng/L, distribution volume (V) （0.68±0.20）L/kg, clearance (CL) （0.38±0.11）L·h-1·kg-1, distribution half-life (t1/2α) （0.05±0.01）h, elimination half-life (t1/2β) （2.53±0.04）h. No significant pharmacokinetic differences were found among CYP2A6*1/*1, *1/*4, and *4/*4 patients.CONCLUSION: In Chinese patients treated with dexmedetomidine, t1/2β is consistent with that published, but t1/2α, V and CL are lower. It is unnecessary to consider the mutation when developing the precision regimen of dexmedetomidine.

Key words: dexmedetomidine, CYP2A6, pharmacokinetics, gene polymorphism

中图分类号:

R614
R969.1

冯淑玲，王凌，王少明，庄捷，齐娟，于荣国. CYP2A6*4基因多态性对右美托咪定药动学的影响[J]. 中国临床药理学与治疗学, 2018, 23(12): 1368-1372.

FENG Shuling, WANG Ling, WANG Shaoming, ZHUANG Jie, QI Juan, YU Rongguo. Effects of CYP2A6*4 gene polymorphism on dexmedetomidine pharmacokinetics[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(12): 1368-1372.

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