芬太尼在腹部手术不同年龄患者的药代动力学研究

Pharmacokinetics of fentanyl in patients of different ages undergoing non-cardiac surgery

目的 研究国产芬太尼在腹部手术不同年龄患者的药代动力学。方法 随机选择腹部手术不同年龄患者 2 4例 ,分为Ⅰ组 (8～ 13岁 ) ,Ⅱ组 (18～ 30岁 )和Ⅲ组 (6 0～ 72岁 ) ,每组 8例。麻醉诱导用芬太尼 5 μg/kg肘静脉注射 ,在注药后 1、2、5、10、2 0、30、6 0、12 0、2 40、36 0min分别抽取桡动脉血标本 ,用GC/MS检测血浆芬太尼浓度 ,3P87软件包计算药代动力学参数。结果 三组患者注射芬太尼后的血药浓度 时间曲线均可用开放性三室模型完整描述 ,血浆芬太尼浓度和t1/ 2 β为Ⅰ组 <Ⅱ组 <Ⅲ组 (P <0 0 5 ) ,CL为Ⅱ组 >Ⅲ组 >Ⅰ组 (P <0 0 5 ) ,t1/ 2 π ,t1/ 2 α几乎没有变化 (P >0 0 5 ) ,Vc和Vd在Ⅰ组与Ⅱ、Ⅲ组有显著性差别 (P <0 0 5 ) ,经体重校正后三组间无显著性差别 (P >0 0 5 )。年龄与t1/ 2 β和CL明显相关 (P <0 0 5 )。 结论 从药代动力学特征得知 ,临床应用芬太尼在儿童可遵循成人的用药原则 ,而在老年人由于t1/ 2 β的延长和CL的降低 。

Objective The purpose of this study was to determine the effects of different ages on pharmacokinetics of fentanyl in patients undergoing non-cardiac surgery.Thus fentanyl may be used reasonally and safely in clinical practice.Methods Twenty-four patients undergoing abdominal surgery were divided into 3 age groups.Each group had eight patients.The age of the patients in group Ⅰ ranged from 8-13 years, in group Ⅱ 18-30 years and in group Ⅲ 60-72 years.Blood samples were obtained from radial artery 1,2,5,10,20,30,60,180 and 240 min following a bolus injection of fentanyl 5μg·kg -1.Plasma fentanyl concentration was determined by GC-MS methods.The pharmacokinetic parameters were calculated using 3P87 computer program.Results Plasma fentanyl concentration reached its peak rapidly following a bolus injection.The plasma concentration versus time curve was fitted to three-compartment open modle using triexponential equation.Although the patients of different age groups received equivalent dose of fentanyl (5μg·kg -1), plasma concentration was higher in elderly patients.This resulted from a prolonged t 1/2β in the elderly patients (group Ⅲ).Vc and Vd increased significantly in group Ⅱ and Ⅲ patients (P<0.05).t 1/2π and t 1/2α were similar in three groups (P>0.05).CL decreased markedly in group Ⅲ (P<0.05). Significant correlations were found between age and both t 1/2β and CL(P<0.05).Conclusions Use of fentanyl in children may follow the guidelines suggested for adults. In elderly the dose of fentanyl should be reduced to some degree because of prolonged t 1/2β and decreased CL.