Liu Dan, Wang Peng-cheng, Qi Xian-rong, Zou Qiang, Zou Ying-hua, Hong Hong
School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Yao Xue Xue Bao. 2006 Aug;41(8):778-83.
To investigate the pharmacokinetics of doxorubicin alginate microspheres (DOX-AM) in vivo after hepatic arterial embolization.
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.
The values of T1/2, AUC, Cmax, 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.
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.
研究阿霉素海藻酸盐微球（DOX-AM）经肝动脉栓塞后在体内的药代动力学。
选用中国小型猪作为实验动物。在对肝动脉肝内分支进行血管造影和超选择性插管后，分别采用DOX-AM进行经导管肝动脉化疗栓塞（TACE，实验组）、碘油和阿霉素（阿霉素-碘油，对照组1）以及阿霉素静脉输注（对照组2）。化疗栓塞或静脉输注后，在不同时间间隔采集血液。采用高效液相色谱法测定血浆中的药物浓度，并计算药代动力学参数。
DOX-AM的T1/2、AUC、Cmax和MRT值与对照组1和对照组2有显著差异。栓塞后，DOX-AM栓塞在血管内，8周时仍滞留于此。数字减影血管造影（DSA）和计算机断层扫描（CT）显示栓塞效果可靠。组织学检查表明，所有组的肝脏损伤均为短暂性改变（P<0.05），并在两周内恢复。肝脏损伤程度依次增加：阿霉素<DOX-AM<阿霉素-碘油。
DOX-AM在肝脏中显示出明确的药物缓释特性，并增加了栓塞后阿霉素在体内的滞留时间和浓度。
