【摘要】：目的:建立大鼠左旋多巴(levodopa,LD)群體藥動(dòng)學(xué)模型,考察LD藥動(dòng)學(xué)參數(shù)的影響因素。方法:14只大鼠隨機(jī)分為高、低兩個(gè)劑量組,單次灌胃給予多巴絲肼片。采用腦微透析技術(shù)收集大鼠紋狀體細(xì)胞外液透析液,同時(shí)采集外周血;高效液相色譜-電化學(xué)法測(cè)定透析液及血漿LD濃度,并利用非線性混合效應(yīng)模型(Nonlinear mixed effect model,NONMEM)進(jìn)行群體藥動(dòng)學(xué)數(shù)據(jù)分析。結(jié)果:建立了包含大鼠個(gè)體間變異、個(gè)體自身變異及體質(zhì)量、給藥劑量等固定效應(yīng)參數(shù)的統(tǒng)計(jì)學(xué)模型,原始數(shù)據(jù)估算的參數(shù)值均位于Bootstrap估算參數(shù)值的2.5%~97.5%范圍內(nèi),視覺(jué)預(yù)測(cè)評(píng)估法顯示建模大鼠外周血和中樞紋狀體LD濃度基本位于90%百分位數(shù)范圍之內(nèi),所建立的最終模型穩(wěn)定、有效、且有較強(qiáng)的預(yù)測(cè)能力。體質(zhì)量可影響LD藥動(dòng)參數(shù)K32。結(jié)論:建立的群體藥動(dòng)學(xué)模型能較好地描述LD在大鼠中樞及外周血的藥動(dòng)學(xué)特點(diǎn)。大鼠給藥劑量對(duì)LD藥動(dòng)參數(shù)無(wú)影響,體質(zhì)量可影響LD藥動(dòng)參數(shù)。
[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，

本文編號(hào)：2478000