国产舒芬太尼在腹部外科手术患者的药代动力学研究

目的 观察腹部外科手术患者国产舒芬太尼单次静脉注射的药代动力学特征.方法 随机选择腹部外科手术患者10例,ASA Ⅰ、Ⅱ级,年龄51～65岁,体重58～68 kg.全身麻醉后经前臂一次性静脉注射国产舒芬太尼2 μg,于注药后1、3、5、10、20、30、60、120、180、240 min和360 min采集桡动脉抗凝全血3ml,离心后吸取血浆1 ml注入真空试管中,-80℃低温保存待测.用液相色谱-质谱联用法测定血浆舒芬太尼浓度,3P97药理学程序判别房室模型并计算药代动力学参数:中心分布容积(Vc),表观分布容积(Vd),快速分布半衰期(t1/2π)、缓慢分布半衰期(t1/2α)、排除半衰期(t1/2β),常数(P、A、B、π、α、β)和速率常数(k10、k12、k21、k13、k31)、清除率(CL)和血药浓度与时间曲线下面积(AUC)等.结果 国产舒芬太尼在腹部手术患者的血药浓度与时间曲线可用三指数函数方程表示:Cp(t)=2.86e-0.8241t+0.75e-0.0604t+0.14e-0.0050t.主要药代动力学参数t1/2π=(1.29±0.81)min、t1/2α=(12.20±2.84)min,t1/2β=(150.50±48.71)min,Vc=(0.552±0.104)L/kg、Vd=(9.008±0.754)L/kg,CL=(0.044±0.011)L/(kg·min)和AUC=(47.58±11.88)ng/(ml·min).结论 国产舒芬太尼在腹部外科手术患者的药代动力学符合三室开放模型,其药代动力学特征与其临床药理学特性相一致.

Pharmacokinetics of domestic sufentanil in Chinese patients undergoing abdominal surgery

Objective To study pharmacokinetics of domestic sufentanil as a single intravenous injection in Chinese patients undergoing abdominal surgery. Methods Ten patients undergoing abdominal surgery, ASA Ⅰ-Ⅱ grade,age from 51 to 65 years old,weighing from 58～68 kg were studied. Intravenous and intra-arterial cannulae were placed in advance. After general anesthesia, sufentanil 2 μg/kg was administered as a rapid bolus intravenously. Blood samples were obtained at 1,3,5,10,20,30,60,120,180,240 and 360 min after sufentanil injection. Plasma was separated from blood samples immediately and stored at -80 ℃ until assayed. Plasma concentration of sufentanil were determined by liquid chromatography mass spectrometry, pharmacokinetic parameters were calculated by 3P97 pharmacology program:central volume of distribution(Vc), apparent volume of distribution (Vd), rapid distribution half-life(t1/2 π), slow distribution half-life(t1/2 α), terminal elimination half-life(t1/2 β),speed constant(P, A, B, π, α, β, k10, k12, k21, k13, k31), clearance(CL)and area under curve(AUC)and so on. Results Pharmacokinetics of sufentanil in patients ndergoing gastrectomy was best fitted to three-compartment open model,the tri-exponential equation :Cp(t)= 2. 86e-0.8241t + 0.75e-0.0604t + 0.14e-0.0050t. Main pharmacokinetic parameter t1/2π =(1.29 ± 0.81)min, t1/2α =(12.20 ± 2.84)min, t1/2β =(150.50 ±48.71)min,Vc =(0.552 ±0.104)L/kg,Vd =(9.008 ±0. 754)L/kg,CL =(0.044 ±0. 011)L/(kg · min)and AUC =(47.58 ±11.88)ng/(ml · min). Conclusions Pharmacokinetics of domestic sufentanil in patients undergoing abdominal surgery was best fitted to three-compartment open model, and the pharmacokinetic characteristics of sufentanil were consistent with its clinical pharmacology.