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Pharmacokinetics of dexmedetomidine in Chinese post-surgical intensive care unit patients.

Abstract：

BACKGROUND:Dexmedetomidine is a rather new drug in China. We sought to describe the pharmacokinetics of dexmedetomidine in patients requiring post-operative sedation and ventilation in our surgical intensive care unit. METHODS:Twenty-two patients received post-operative infusions of dexmedetomidine at 6 μg/kg/h for 10 min, followed by 0.4 μg/kg/h for 350 min. Venous blood samples were drawn and assayed for plasma concentration. The pharmacokinetics were analysed using a nonlinear mixed-effect model with an interindividual and intraindividual error model. An initial estimation was performed to determine which of the one-, two- or three-compartment models is best to describe the concentration-time data. The covariates age, gender, weight, height, lean body mass (LBM), body surface area (BSA) and body mass index (BMI) were tested for significant effects on parameters using a stepwise forward addition and backward elimination approach. Covariate effects were judged based on changes in the objective function value (OFV). RESULTS:The pharmacokinetics of dexmedetomidine were best described by a three-compartment model. The model was further improved when height was a covariate of systemic clearance (Cl1), with a decrease in OFV by -13.56 (P<0.01). From the heights of 155-178 cm, Cl1 increased by approximately 143%. The final pharmacokinetic parameter values were as follows: V1 =63.4 l, V2=41.3 l, V3 =284.3 l, Cl1=0.47×(height/160 cm)(6.42) l/min, Cl2=2.43 l/min and Cl3=0.086 l/min. CONCLUSIONS:This study identified (i) the effect of height on the pharmacokinetics of dexmedetomidine; (ii) that there is no influence of age, gender, weight, LBM, BSA and BMI on pharmacokinetic parameters; and (iii) it established a preliminary population pharmacokinetic model for Chinese patients.

journal_name

Acta Anaesthesiol Scand

journal_title

Acta anaesthesiologica Scandinavica

authors

Lin L,Guo X,Zhang MZ,Qu CJ,Sun Y,Bai J

doi

10.1111/j.1399-6576.2010.02392.x

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

359-67

issue

3

eissn

0001-5172

issn

1399-6576

journal_volume

55

pub_type

杂志文章

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