多柔比星海藻酸钠微球体内肝动脉栓塞的药代动力学和评价

目的对多柔比星海藻酸钠微球(DOX-AM)进行体内肝动脉栓塞后药代动力学的研究。方法以中华小型猪为实验动物，动脉造影后超选择至肝动脉分支，实验组行DOX-AM肝动脉化疗栓塞，两个对照组分别行碘油多柔比星(DOX-lipiodol)肝动脉化疗栓塞和单纯多柔比星(DOX)肝动脉灌注；定时取实验动物的外周静脉血，采用高效液相色谱法(HLPC)测定其血药浓度并进行药代动力学方面的相关统计处理。栓塞前后进行影像学检查。结果DOX-AM与单纯DOX溶液灌注和DOX-lipiodol栓塞相比，在血浆半衰期﹑药时曲线下面积、最大血药浓度和平均滞留时间等方面均呈现明显的差异性；肝组织学检查证实DOX-AM栓塞后阻塞在血管内并停留一定时间。数字减影血管造影(DSA)和计算机断层扫描(CT)检查显示栓塞效果可靠，组织学检查显示对肝脏的副作用按碘油多柔比星栓塞、多柔比星海藻酸钠微球栓塞及单纯DOX肝动脉灌注的顺序下降。结论DOX-AM在肝脏行动脉栓塞后，具有明显的缓释作用，可以显著延长药物在体内的停留时间，对肝脏的副作用小于碘油多柔比星肝动脉栓塞。

Pharmacokinetics of doxorubicin alginate microspheres and evaluation of its hepatic arterial embolization in vivo

Aim To investigate the pharmacokinetics of doxorubicin alginate microspheres(DOX-AM) in vivo after hepatic arterial embolization.Methods China miniature pigs were chosen as the experimental animals.Transcatheter hepatic arterial chemoembolization(TACE) with DOX-AM(experimental group),lipiodol and DOX(DOX-lipiodol,control group 1),and infusion with DOX(control group 2) were performed after angiography and superselection of an intrahepatic branch of hepatic artery.After chemoembolization or infusion,the blood was collected at different time intervals.Drug concentration in plasma was measured by HLPC and the parameters of pharmacokinetics were calculated.Results The values of T_1/2,AUC,C_max,and MRT of the DOX-AM were significantly different from those of control group 1 and control group 2.After embolization,the DOX-AM embolized in the vessel and still retained there at 8 weeks.The digital subtraction arteriography(DSA) and computerized tomography(CT) showed the reliable embolization results.The histological examination indicated that the liver damnifications were changed transitorily in all groups(P<0.05) and were recovered within two weeks.The liver damnifications increased in following order: DOX < DOX-AM < DOX-lipiodol.Conclusion DOX-AM showed definite property of delayed release of drug in liver,and increased the retention time and concentration of DOX after embolization in vivo.