Impact of CYP2A6 gene polymorphism on the pharmacokinetics of dexmedetomidine for premedication. Issue 9 (2nd September 2018)

• Record Type: Journal Article
• Authors: Wang, Ling; Wang, Shaoming; Qi, Juan; Yu, Rongguo; Zhuang, Jie; Zhuang, Boyang; Lou, Yongming; Ruan, Junshan; Ye, Hong; Lin, Fangfang
• Is Part Of: Expert review of clinical pharmacology. Volume 11:Issue 9(2018)
• Page Start: 917
• Page End: 922
• Publication Date: 2018-09-02
• Subjects: Dexmedetomidine -- gene polymorphisms -- premedication -- pharmacokinetics -- CYP2A6; Clinical pharmacology -- Periodicals; 615.105
• DOI: 10.1080/17512433.2018.1510312
• Languages: English
• ISSNs: 1751-2433

Abstract

ABSTRACT: Background : Dexmedetomidine is a widely used sedative in clinic, which is mainly metabolized by cytochrome P450 2A6 (CYP2A6). Dexmedetomidine was rarely reported for off-label usage of premedication, but lacking relevant pharmacokinetic investigations. Therefore, our study determined the dexmedetomidine pharmacokinetics of CYP2A6*4 allele in Chinese patients pretreated with dexmedetomidine whose mutation frequency of CYP2A6*4 are high, in order to provide clinical references. Methods : Thirty-one elective surgery patients received premedication with 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 : 9 patients were *1/*4 or *4/*4, and 22 patients were *1/*1. The main pharmacokinetic parameters were area under curve (AUC) 1396.19 ± 332.47h· ng· l −1, peak blood concentration (Cmax ) 495.50 ± 104.90ng· l −1, distribution volume (V) 0.68 ± 0.20 L/kg, clearance (CL) 0.38 ± 0.11 L/h/kg, distribution half-life (t1/2α ) 0.05 ± 0.01h, elimination half-life (t1/2β ) 2.53 ± 0.04h. No significant pharmacokinetic differences were found among CYP2A6*1/*1, *1/*4, and *4/*4 patients. Conclusions : In Chinese patients pretreated with dexmedetomidine, T1/2β was consistent with that published, but T1/2α, V and Cl were lower. It was unnecessary to consider the mutation when developing the precision regimen of dexmedetomidine.