阿霉素-明胶微球经犬胃左动脉栓塞药代动力学研究

目的 研究阿霉素明胶微球(ADM-GMS)犬胃左动脉栓塞灌注在血浆及局部组织中的药代动力学。方法 15只健康杂种犬随机分为3组，每组5只。A组：单纯ADM经外周静脉给药；B组：单纯ADM经胃左动脉给药；C组：ADM-GMS经胃左动脉栓塞灌注。给药后定时从胃冠状静脉和外周静脉抽血，用高效液相色谱(HPLC)测定ADM的时间血中药浓度。48h后，将犬处死，测定胃组织含药浓度，并对C组犬加行胃组织病理学检查。结果 B组仅形成-过性血浆高浓度。C组ADM释放缓慢，峰浓度低，半衰期长，1h内血浆中药物浓度曲线下面积(AUC)是B组的77．5％。48h后C组胃组织含药浓度分别是B组和A组的2．4倍和4．4倍。结论 ADM-GMS用于栓塞化疗，可以提高局部组织的药物浓度，延长其在靶器官的滞留时间，并可减少对周围组织的毒副作用。

Study of Pharmacokinetics of Adriamycin-Gelatin Microspheres Embolization via Dogs'' Left Gastric Artery

Objective To study the pharmacokinetics of plasma and local tissue after adriamycin-gelatin microspheres (ADM-GMS) perfution and embolization via dogs' left gastric artery.Methods Fifteen healthy crossbreeding dogs were divided into three groups with five dogs each group.The dogs were given a peripheral vein injection of ADM (group A), the left gastric artery injection of ADM (group B), and the left gastric artery injection of ADM-GMS (group C).Blood was drawed from the gastric coronal vein and the peripheral vein on time after administration, the blood concentration of ADM was determined with HPLC.Executing all dogs in the 48h, drug concentration in their gastric tissue was determined and the pathological changes of the gastric tissue of group C were examined.Results The temporarily high level of plasma drug was observed in group B.ADM releasing slowly was observed in group C with low peak concentration and long half life.The plasma concentration (AUC) in 1h for group C was 77.5% of group B.The drug concentration in gastric tissue of group C was 2.4 times that of group B and 4.4 times that of group A.Conclusion ADM-GMS used for chemoembolization could improve the drug concentration of ADM in local tissue, prolong the acting time in target organ and reduce the side-effect to surrounding tissue.