阿霉素不同剂型经肝动脉给药治疗肝癌的体内药动力学研究  

A study of the pharmacokinetics and biodistribution of doxorubicin in different formulation injected to hepatic artery for hepatocellular carcinoma

作　　者：韩国宏[1,2] 郭庆林[1,2] 郭宇良 邓敬兰[1,2] 杜镐[1,2] 盛启光 

机构地区：[1]第四军医大学西京医院 [2]西安市药品检验所

出　　处：《癌症》1998年第3期194-196,共3页Chinese Journal of Cancer

摘　　要：目的：观察阿霉素以不同剂型肝动脉给药后的药代动力学和生物学分布。方法：２３例肝癌经肝动脉分别注入单纯阿霉素（Ａ组ｎ＝５）；阿霉素与碘油混合液（Ｂ组ｎ＝５），阿霉素与碘油混合并制成乳剂（Ｃ组ｎ＝７），或Ｃ组之乳剂加用明胶海绵栓塞（Ｄ组ｎ＝６）。用高效液相色谱仪测定阿霉素外周血药浓度，对其中１２例（Ａ、Ｂ、Ｃ和Ｄ组各３例），用ＥＣＴ测定肝脏的放射性强度。结果：肝动脉单纯注入阿霉素，仅形成一过性血浆高浓度，无器官优势分布特点。阿霉素碘油简单混合，未能发挥碘油的载体特点，出现的只是阿霉素和碘油各自的单一作用，与单纯注入阿霉素的疗效无显著差别。阿霉素碘油乳剂，能明显降低血药峰值浓度，延缓药物释放，并能选择性分布于肝肿瘤内，达到了靶向治疗肝癌的目的。加用明胶海绵栓塞，使上述作用更加明显。结论：从药代动力学和生物学分布角度分析，抗癌药碘油乳剂并用明胶海绵是最好的肝动脉化疗栓塞治疗肝癌的方法。Purpose: To observe the pharmacokinetics and biodistribution of doxorubicin in different formulation injected to hepatic artery for hepatocellular carcinoma. Methods: Twenty-three patients with hepatocellular carcinoam were given an intraarterial injection of doxorubicin alone (group A, n=5), a simple mixture of doxorubicin in aqueous solution with lipiodol (group B, n=5), an emulsion of doxorubicin with lipiodol (group C, n=7), or chemoembolization with the same emulsion followed by gelatin sponge particles (group D, n=6) respectively. The pharmacokinetics and biodistribution of doxorubicin were studied respectively by measurements of the blood level of doxorubicin after injection and by examination of the scintigrams and radioactivity with ECT. Results: Doxorubicin injected alone resulted in a temporarily high elvel of drug without predominant uptake of organs. The simple mixture of doxorubicin with lipiodol, in which lipiodol did not play the characteristics role as a carrier, only had the effects of doxorubicin and lipiodol seporately, and did not have significant difference from doxorubicin alone. The emulsion of doxorubicin with lipiodol lowered the peak concentration of doxorubicin, prolonged its release and remained in tumors for a longer period of time, therefore targeting of drug to the tumor could be achieved. These ameliorations were more pronounced after embolization with gelatin sponge particles. Conclusion: From pharmacokinetics and biodistribution standpoints, the emulsion of doxorubicin with lipiodol associated with gelatin sponge embolization is the best method of transcatheter hepatic arterial chemoembolization for hepatocellular carcinoma.

关 键 词：肝肿瘤 药物疗法 药物代谢动力学 阿霉素 

分 类 号：R735.705[医药卫生—肿瘤] R979.14[医药卫生—临床医学]