猪静注、肌注氟尼辛葡甲胺的药物动力学研究

Pharmacokinetics of Flunixin Meglumine After Intervenous,Intramuscular Administration in Pigs

【目的】为了研究氟尼辛葡甲胺在健康猪体内的药动学。【方法】14头健康猪,按照随机拉丁方设计,进行单次不同给药剂量(2.2,1.1mg·kg-1bw)静注和肌注。血浆样品经乙腈沉淀血浆蛋白,高速离心,用反相高效液相色谱法测定猪血浆中氟尼辛葡甲胺的浓度,3P97药动学计算软件处理血浆药物浓度-时间数据。【结果】健康猪静注给药的药时数据适合二室开放模型,2.2、1.1mg·kg-1bw剂量组主要药动学参数分别为:t1/2α(0.49±0.03)h,(0.58±0.07)h;t1/2β(6.28±0.13)h,(7.37±0.59)h;V/F(0.01±0.001)L·kg-1,(0.01±0.002)L·kg-1;CL(0.01±0.002)L·h-1,(0.01±0.002)L·h-1;AUC(237.73±52.46)μg·h·ml-1,(147.71±36.76)μg·h·ml-1。健康猪肌注给药的药时数据适合一级吸收二室模型,2.2mg·kg-1bw、1.1mg·kg-1bw剂量组主要药动学参数为:t1/2α(0.90±0.07)h,(0.86±0.10)h;t1/2β(8.79±0.85)h,(9.60±0.10)h,V/F(0.02±0.004)L·kg-1,(0.02±0.003)L·kg-1;CL(0.01±0.002)L·h-1,(0.01±0.003)L·h-1;AUC(174.63±45.84)μg·h·ml-1,(112.42±31.19)μg·h·ml-1。【结论】氟尼辛葡甲胺在健康猪体内肌注的主要药动学特征为吸收迅速,达峰时间短,生物利用度较高,半衰期较长。

【Objective】The objective was to study the pharmacokinetics of flunixin meglumine（FM）in healthy pigs.【Method】A single intravenous,intramuscular administration of the drug at the dose of 2.2 mg·kg^-1bw and 1.1 mg·kg^-1bw to 14 pigs in an open randomized crossover test.Blood samples were collected at different intervals after administration and concentrations of FM were determined by HPLC method with a limit of detection of 0.1μg·ml^-1.【Result】The main pharmacokinetic parameters were as follows：t1/2α 0.49±0.03 h,0.58±0.07 h;t1/2β（6.28±0.13）h,（7.37±0.59）h;V/F（0.01±0.001）L·kg^-1,（0.01±0.002）L·kg^-1;CL（0.01±0.002）L·h^-1,（0.01±0.002）L·h^-1;AUC（237.73±52.46）μg·h·ml^-1,（147.71±36.76）μg·h·ml^-1.The drug concentration-time data were fitted to a two-compartment model with first order absorption after single i.m.administration in pigs.The main pharmacokinectic parameters were as follows：t1/2α（0.90±0.07）h,（0.86±0.10）h;t1/2β（8.79±0.85）h,（9.60±0.10）h;V/F（0.02±0.004）L·kg^-1,（0.02±0.003）L·kg^-1;CL（0.01±0.002）L·h^-1,（0.01±0.003）L·h^-1;AUC（174.63±45.84）μg·h·ml^-1,（112.42±31.19）μg·h·ml^-1.【Conclusion】The results of present studies showed that FM was rapidly absorbed,extensively distributed and slowly eliminated in pigs.The drug was completely absorbed after single i.m administration and a good bioavailability in pigs.