氟尼辛葡甲胺在黄牛血浆、组织液和炎症渗出液中的药动学

Pharmacokinetics of flunixin meglumine in plasma,exudate and transudate in yellow cattle

6头成年健康黄牛，皮下埋置组织笼后，建立急性炎症模型，以2．2mg／kg剂量单次快速静注氟尼辛葡甲胺，高效液相色谱（HPLC）-紫外检测法测定血浆、组织液和炎症渗出液中氟尼辛葡甲胺的质量浓度，用WinNonlin药动学软件的“非房室模型”分析药动学参数。结果显示：静注氟尼辛葡甲胺后，黄牛血浆中药物质量浓度下降迅速，体内分布广泛，消除半衰期为（t1/2λz）为5．34h，体清除率（CL）为0．18L／kg，表观分布容积（Vd）为1．37L／kg，药-时曲线下面积（AUC）为12．33μg·h／mL；氟尼辛葡甲胺广泛地分布到组织液和炎症渗出液中，但是渗透速度慢。组织液和炎症渗出液中药物的平均达峰时间（t max）分别为7．12h和3．25h，峰浓度（Cmax）分别为0．65mg／L和1．44mg／L，组织液和炎症渗AUC与血浆AUC比值（AUC ratio）分别为118％和214％。以上数据表明，氟尼辛葡甲胺分布到炎症组织的能力强于正常组织，组织液和炎症渗出液中药物消除均速度慢于血浆，每天静脉注射2．2mg／kg氟尼辛葡甲胺可以在黄牛体内发挥有效作用。

The pharmacokinetics of flunixin meglumine （FM） in yellow cattle was investigated to provide references for clinical rational use of drugs. FM （2. 2 mg/kg） was administered intravenously （i. v. ） as a single dose to 6 yellow cattle prepared with subcutaneous tissue-cages in which an acute inflammatory reaction was stimulated. FM concentrations in these samples were determined by use of high-pressure liquid chromatography with an ultraviolet detector. Plasma,exudate and transudate concentration data was analyzed by the noncompartment model of WinNonlin 6.1 software. After i. v. administration, FM elimination was relatively faster and it was widely distributed throughout the body. The mean elimination half-life （t1/2λz） was 5.34 h, the total body clearance （CL） was 0. 18 L/kg,the volume of distribution （Vd） was 1.37 L/kg,and the area under the plasma concentration-time curve （AUC） was 12.33 μg · h/mL; FM distributed well into exudate and transudate although penetration was slow. A maximum drug concentration （Cmax） of 1. 44 mg/L in exudate occured at 3.25 h and a Cmax Of 0. 65 mg/L in transudate at 7.12 h,The AUC ratio of transudate AUC and exudate AUC to plasma AUC were 118% and 214%, respectively. Results indicate that FM has greater penetration into inflamed tissue fluid （exudate） than into non-inflamed transudate,and elimination of FM from exudate and transudate was slower than from plasma. A dosage of 2.2 mg/kg by i. v. administration to yellow cattle with 24 h dosing interval may he adequate to provide effective treatment.