国人老年患者靶控输注丙泊酚的群体药代动力学

摘要

Aim To investigate the population pharmacokinetics of propofol administered by TCI in Chinese elderly patients. Methods Thirty-two patients with ASA Ⅰ-Ⅱ, 65-82 years old, undergoing selective lower abdominal operation were studied. Propofol was administered by target-controlled infusion with Marsh parameter. The target plasma concentration was 3 μg·mL-1. Radial arterial blood samples were collected and analyzed by reversed phase HPLC with fluorescence detection. Population pharmacokinetic modeling was performed using NONMEM. Inter-individual variability and intra-individual variability of propofol were estimated for clearances and volumes of distribution. The effects of age, body weight, lean body mass, gender, height, hemoglobin, total protein, albumin, creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were investigated. The effects of coadministered opioid drugs were also studied. Results The pharmacokinetics of propofol in the Chinese elderly patients was best described by a three-compartment open model. Lean body mass was found to be a covariate for system clearance at significant level (P<0.005). The clearance decreased linearly with age as well (P<0.005). The apparent volume of distribution for deep peripheral compartment (V3) was influenced by gender. Elderly female patients showed a higher value for V3. Conclusion The pharmacokinetics of propofol administered by TCI in Chinese elderly patients can be well described by a three-compartment open model. Inclusion of age, lean body mass and gender as covariates significantly improved the model. To ensure the accuracy and precision of target-controlled infusion, the population pharmacokinetic model applied to the individual patient should be adjusted reasonably.%目的研究丙泊酚靶控输注用于国人老年患者的群体药代动力学.方法 32例择期下腹部开腹手术的患者,ASAⅠ-Ⅱ级,年龄65～82岁的老年患者,采用靶控输注方式(以血浆浓度为靶)输注丙泊酚,丙泊酚血浆浓度为3 μg·mL-1.术中取桡动脉血,以反向高效液相色谱-荧光法测定丙泊酚的血浆浓度.用NONMEM软件分析丙泊酚的药代动力学参数.结果国人老年患者靶控输注丙泊酚的药代动力学过程符合三室开放模型,年龄、瘦体重对中央室清除率有影响,性别对第三分布容积有影响.结论年龄、瘦体重、性别对国人老年患者丙泊酚的药代动力学参数有影响.群体药代动力学参数应用于个体时,应根据个体情况相应调整靶控输注的药代动力学参数,以改善靶控输注系统的精确性.