Population pharmacokinetics of a propofol bolus administered in patients with major burns

作者：Yamashita Susumu; Kaneda Kotaro; Han Tae Hyung^*

来源：Burns, 2010, 36(8): 1215-1221.

DOI：10.1016/j.burns.2010.03.003

• Burns
• Propofol
• Population pharmacokinetics
• Nonlinear mixed effect model

Objective In operating theaters and burn units propofol is commonly used for sedation and anesthesia in patients with major burns This study determined the population pharmacokinetics of propofol in burns and identified clinically significant covariates
Method Seventeen adults age 42 +/- 10 (mean +/- SD) years with 41 +/- 19% total body surface area burns were enrolled at 16 +/- 14 days after burn Non burn adults (n = 19) served as controls After an intravenous bolus of 2 mg/kg propofol the plasma concentration was determined at designated times for up to 4 5 h Concentration-time profiles were analyzed using nonlinear mixed effect modeling
Results A three compartment model gave the best fit The volume of distribution of the central compartment (V(1)) was considerably greater in the burned than non burned group (48 4 L us 27 6 L respectively) The clearances of the central (CL(1)) and slow peripheral (CL(3)) compartments were higher in burn patients (4 2 L/min vs 1 7 L/min and 3 6 L/min vs 1 1 L/min respectively) Adding the covariates BURN to V(1) CL(1) and CL(3) and WT (weight) to CL(1) significantly improved the model performance
Conclusion The pharmacokinetic characteristics of a propofol bolus administered in patients with major burns were enhanced clearance and expanded volume of distribution BURN and WT were the important covariates For sedation or anesthesia induction a higher than recommended dose of propofol may be required to maintain therapeutic plasma drug concentrations in

• 出版日期2010-12