肥胖程度对顺式阿曲库铵药物代谢动力学参数的影响

Pharmacokinetics of cisatracurium in the patients with different obesity underwent general anesthesia

目的考察不同程度肥胖患者接受顺式阿曲库铵全麻时的药物代谢动力学特征。方法收集2016年6月至2017年4月我院收治的择期行腹腔镜胃旁路手术的患者60例,根据体质量指数分为体质量正常组(n=14)、轻度肥胖组(n=14)、中度肥胖组(n=17)和重度肥胖组(n=15)。收集所有受试者接受顺式阿曲库铵后0、5、10、15、30、60、90、120、180、240、360及480 min的血浆,采用高效液相色谱法检测血浆中顺式阿曲库铵血药浓度及药物代谢动力学参数。结果该色谱法的精密度、准确度、稳定性和回收率均较好。与体质量正常组相比,轻度、中度和重度肥胖组给药后10、15、30和60 min的血药浓度均有不同程度降低(P<0.05);与体质量正常组相比,轻度、中度和重度肥胖组药物分布半衰期(t_(1/2a))和从零时间到所有原形药物全部消除这段时间的药-时曲线下总面积(AUC_(0-∞))不同程度减低(P<0.05),表观分布容积和清除率不同程度增高(P<0.05)。结论不同肥胖程度患者接受顺式阿曲库铵全麻的药物代谢动力学特征均符合开放性二室模型,且随患者肥胖程度增加,顺式阿曲库铵t1/2a缩短,AUC_(0-∞)减少。

Objective To investigate the pharmacokinetics of cisatracurium in the patients with different obesity underwent general anesthesia. Methods A total of 60 patients underwent laparoscopic cholecystectomy from June 2006 to April 2017 were enrolled and divided into normal weight group(n=14), mild obesity group(n=14), moderate obesity group(n=17) and severe obesity group(n=15) based on their body mass index. The plasma concentration at administration 0, 5, 10, 15, 30, 60, 90, 120, 180, 240, 360 and 480 min, and the pharmacokinetics parameters of cisatracurium were measured by high performance liquid chromatography(HPLC). Results The precision, accuracy, stability and recovery rate of HPLC were all good. Compared with normal weight group, the plasma concentration of mild, moderate and severe obesity group at administration 10, 15, 30, 60 were decreased in obesity dependent manner, the t_(1/2α) and AUC_(0-∞) were decreased, and the Vd and CL were increased in obesity dependent manner(P<0.05). Conclusion The pharmacokinetics of cisatracurium in the patients with different obesity is in accordance with the 2-compartment open model: as the increase of obesity, the t_(1/2α) shorten and AUC_(0-∞) decrease.