阿霉素羧甲基葡聚糖微球犬肝动脉栓塞后阿霉素的体内过程

研究了阿霉素羧甲基葡聚糖微球经肝动脉栓塞后的体内动力学过程、靶向特征和微球在体内的肝动脉栓塞效果。对犬进行肝动脉栓塞实验,并与肝动脉阿霉素(ADM)溶液灌注组进行对照。用HPLC荧光检测外周静脉和组织中药物浓度。结果表明:微球组峰浓度为0.558μg/ml,溶液组为1.013μg/ml;微球组的T_1/2(α),T_1/2(β)和MRT分别为溶液组的2.82,3.19和1.28倍。栓塞不同部位组织中ADM浓度,微球组分别是溶液组的8.0和9.1倍。动态血管造影表明:肝内外未见侧枝循环形成,栓塞作用持久,16周后微球仍未见完全降解。

STUDIES ON PHARMACOLOGIC DISPOSITION OF ADRIAMYCIN IN DOG AFTER HEPATIC ARTERIAL EMBOLIZATION WITH ADRIAMYCIN CARBOXYMETHYLDEXTRAN-MICROSPHERES

The ion exchange adriamycin carboxymethyl-dextran-microspheres (AD-CMDMS) was chosen as a model preparation. Pharmacokinetics, targeting and embolization effects of the microspheres were studies after hepatic arterial embolization in vitro in dogs.After hepatic arterial infusion, the concentrations of ADM in peripheral vein blood and hepatic tissue were determined by HPLC. The peak concentrations were (0.558 μg/ml for AD-CM-DMS and 1.013 μg/ml for ADM solution. T_1/2 (α), T_1/2 (β) and MRT of AD-CM-DMS were respectively 2.82, 3. 19 and 1.28 times as much as those of ADM solution. At the target site, the tissue concentrations of AD-CM-DMS were respectively 8.0 and 9.1 times those of ADM solution. The dynamic vessel angiography revealed no external and internal collaterals and no complete degradation of ADCM-DMS after sixteen weeks was observed. These results suggest that AD-CM-DMS are useful as embolic agent for the treatment of hepatic career. It could facilitate intensive chemotherapy with minimum systematic side effect.