丙泊酚在重度烧伤兔高代谢期的药代动力学研究

目的探讨丙泊酚在危重烧伤兔高代谢期的药代动力学特点。方法将24只新西兰大白兔随机分为烧伤高代谢期组（H组）和对照组（C组）,每组12只。将H组兔制成30%TBSA的Ⅲ度烫伤,1周后单次静脉注射5.1mg/kg丙泊酚,利用高效液相色谱仪（HPLC）检测不同时间点兔血浆丙泊酚浓度,用3P97药代动力学软件拟合选择房室模型,计算药代动力学参数;对两组血浆药物浓度和药代动力学参数进行统计学分析。结果两组均符合二室开放模型;H组血浆丙泊酚浓度在1～30min各点明显低于C组,有显著性差异（P＆lt;0.01或P＆lt;0.05）;与C组比较,H组VC、CL、K10增加,T1/2α、T1/2β缩短,AUC、K12、K21等参数降低（P＆lt;0.01或P＆lt;0.05）。结论丙泊酚在危重烧伤兔高代谢期药代动力学参数变化明显,较正常兔分布半衰期、消除半衰期缩短,分布容积增大,清除率显著增加。

Pharmacokinetics of propofol used during hypermetabolic phase in severely burned rabbits

Objective To study the characteristics of propofol pharmacokinetics used during hypermetabolic phase in severely burned rabbit model. Methods Twenty four New Zealand rabbits were randomly divided into hypermetabolic phase group （group H,n=12） and control group （group C,n=12）. Rabbits of group H were scalded with hot water（98℃） full thickness to 30 percent of total body surface area（TBSA）, after one week they were given an intravenous bolus of propofol 5.1mg/kg, the plasma propofol concentrations were determined at 1, 3,5,10,15,20,30,45,60,90minute after injection by high performance liquid chromatography （HPLC）. Data of propofol concentration was analyzed and the compartment model was fitting with 3P97 program, then the best pharmacokinetic parameters and compartment model were chose according to AIC value and F value. Results Ten rabbits finished experiment in two groups respectively. Propofol concentration of group H from 1 to 30 minute was higher than that in the control group. Two groups were well fitted with two-compartment open model： Comparing with group C, VC、CL、K10 of group H increased , T1/2α、T1/2β shortened, AUC、K12、K21 decreased significantly （P 〈 0.01, P 〈 0.05）. Conclusions Pharmacokinetic parameters of propofol evidently changes in severe burns rabbit model during hypermetabolic phase, distribution half time and elimination half time of propofol are shortened, distribution volume and clearance of propofol increase contrast to normal rabbits.