Impact of CYP2A6 gene polymorphism on the pharmacokinetics of dexmedetomidine for premedication.

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 CYP2A64 allele in Chinese patients pretreated with dexmedetomidine whose mutation frequency of CYP2A64 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, peak blood concentration (C) 495.50 ± 104.90ng· l, distribution volume (V) 0.68 ± 0.20 L/kg, clearance (CL) 0.38 ± 0.11 L/h/kg, distribution half-life (t) 0.05 ± 0.01h, elimination half-life (t) 2.53 ± 0.04h. No significant pharmacokinetic differences were found among CYP2A61/*1, *1/*4, and *4/*4 patients.

CONCLUSIONS

In Chinese patients pretreated with dexmedetomidine, T was consistent with that published, but T, V and Cl were lower. It was unnecessary to consider the mutation when developing the precision regimen of dexmedetomidine.