Effects of CYP2A6*4 gene polymorphism on dexmedetomidine pharmacokinetics

doi:10.12092/j.issn.1009-2501.2018.12.009

Abstract

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

CLC Number:

R614
R969.1

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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