盐酸他可林在大鼠体内的药物动力学

PHARMACOKINETICS OF TACRINE IN RATS

研究盐酸他可林（ＴＨＡ）在大鼠体内的药物动力学。方法大鼠分别ｉｖ和ｉｇＴＨＡ４、８、１６ｍｇ．ｇ－１后，用反相高效液相色谱法测定其血药浓度，以ＣＡＰＰ软件拟合其房室模型。用平衡透析法测定血浆蛋白结合率。结果血药浓度—时间关系符合二室模型。静注低、中、高３个剂量后，ｔ１／２（分别为７２、６０、６５ｍｉｎ；曲线下面积（ＡＵＣ）分别为２０、３４、４７ｇｍｉｎ·Ｌ－１；清除率（ＣＬ）分别为０．０５３、０．０６２、０．０９０Ｌ·ｋｇ－１·ｍｉｎ－１，灌胃后ｔ１／２分别为６０、６３、６２ｍｉｎ；ＡＵＣ分别为７、１２、２１ｇｍｉｎ－１；ＣＬ分别为０．１５３、０．１５２、０．２４０Ｌ·ｋｇ－１·ｍｉｎ－１。血浆蛋白结合率为５２％。结论盐酸他可林在大鼠体内的消除较快，个体差异较大。

Objective To study the plarmacokinetics of tacrine(THA)in rats Methods After iv of ig administrationof THA 4,8,16mg·kg 1 in rats,the plasma THA concentration were determinedby reversed phase HPLC,and the pharmacokinetic parameters were calculated by CAPP software.The plasma protein binding rate of THA was measured by equilibrium dialysis.Results The concentration-time curves were adquently described by a two-compartment open model.The main parameters after iv administration of THA 4,8,16mg·kg -1 were t 1/2β 72,60,65min;AUC 20,34,47g·min·L -1 ;CL 0.053,0.062,0.090L·kg -1 ·min -1 ;rcspectively.And the parameters after ig THA were:t 1/2β 60,63,62min;AUC 7,12,21g·kg -1 ·min -1 ,rcspcctivcly.The plasma protein binding rate of THA inrats was 52%.Conclusion The elimination of THA was fast and the individual difference in pharmacokinetics among rats was great.