Ling Wang1, Shaoming Wang1, Juan Qi2, Rongguo Yu3, Jie Zhuang1, Boyang Zhuang4, Yongming Lou5, Junshan Ruan1, Hong Ye1, Fangfang Lin1. 1. a Department of Pharmacy , Fujian Provincial Hospital, Provincial Clinical College of Fujian Medical University , Fuzhou , China. 2. b Second Department of Anesthesiology , Fujian Provincial Hospital, Provincial Clinical College of Fujian Medical University , Fuzhou , China. 3. c Surgery Intensive Care Unit , Fujian Provincial Hospital, Provincial Clinical College of Fujian Medical University , Fuzhou , China. 4. d Center for Certification and Evaluation , Fujian Food and Drug Administration , Fuzhou , China. 5. e Chemical Laboratory , Fujian Institute for Food and Drug Quality Control , Fuzhou , China.
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.
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.