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NONMEM法建立大鼠外周和中枢左旋多巴群体药动学模型

发布时间:2019-05-16 03:56  文章来源:笔耕文化传播
【摘要】:目的:建立大鼠左旋多巴(levodopa,LD)群体药动学模型,考察LD药动学参数的影响因素。方法:14只大鼠随机分为高、低两个剂量组,单次灌胃给予多巴丝肼片。采用脑微透析技术收集大鼠纹状体细胞外液透析液,同时采集外周血;高效液相色谱-电化学法测定透析液及血浆LD浓度,并利用非线性混合效应模型(Nonlinear mixed effect model,NONMEM)进行群体药动学数据分析。结果:建立了包含大鼠个体间变异、个体自身变异及体质量、给药剂量等固定效应参数的统计学模型,原始数据估算的参数值均位于Bootstrap估算参数值的2.5%~97.5%范围内,视觉预测评估法显示建模大鼠外周血和中枢纹状体LD浓度基本位于90%百分位数范围之内,所建立的最终模型稳定、有效、且有较强的预测能力。体质量可影响LD药动参数K32。结论:建立的群体药动学模型能较好地描述LD在大鼠中枢及外周血的药动学特点。大鼠给药剂量对LD药动参数无影响,体质量可影响LD药动参数。
[Abstract]:Aim: to establish a population pharmacokinetics model of levodopa (levodopa,LD) in rats and to investigate the influencing factors of pharmacokinetics parameters of LD. Methods: fourteen rats were randomly divided into two groups: high and low dose groups, and dobutamine tablets were given intragastrically. The extracellular fluid of rat striatum was collected by cerebral microdialysis technique, and the peripheral blood was collected at the same time. The concentrations of LD in dialysate and plasma were determined by high performance liquid chromatography-electrochemical method, and the population pharmacokinetics data were analyzed by using the nonlinear mixed effect model (Nonlinear mixed effect model,NONMEM). Results: a statistical model containing fixed effect parameters such as inter-individual variation, individual self-variation, body mass and administration dose was established. The parameters estimated by the original data were in the range of 2.5% 鈮,

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