肝癌动脉化疗给药方式和剂型对药物代谢动力学影响研究

肝癌是全世界最常见的恶性肿瘤之一，而经导管肝动脉化疗栓塞（TACE）是治疗不能手术的中晚期肝癌的标准手段。从给 药方式上而言，相对于静脉系统化疗及单纯的肝动脉灌注，肝动脉化疗栓塞术，尤其是进行明胶海绵补充栓塞，可明显改善物代 谢动力学参数，既减少外周药物浓度和非靶器官毒性，又能增加局部药物浓度从而增强药物的治疗效果。从剂型上而言，阿霉素 碘化油乳剂能明显降低血药峰值浓度，并能选择性分布于肝脏肿瘤内，达到靶向治疗肝癌的目的。加用明胶海绵补充栓塞，上述 作用会更加明显。肝动脉化疗药微囊栓塞也能取得较明显的物代谢动力学优势，缓释、增加局部浓度、延长作用时间和减轻药物 不良反应。无论外周血药峰值浓度（Cmax）还是曲线下面积（AUC），载药洗脱微球(DEB)栓塞均显著低于阿霉素碘化油乳剂栓塞， 从而取得比传统的化疗栓塞更好的肝癌治疗效果。对不同给药方式及载药剂型的物代谢动力学研究，将对不断提高TACE的疗 效和安全性有重要意义。

Influence of Medicine Method and Dosage Formof Intra-arterial Hepatic Infusion on Pharmacokinetics

Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors in the world, and transcatheter arterial chemoembolization (TACE) is the standard therapy for advanced HCC that cannot be operated. On the medicine method hand, compared with the systemic chemotherapy and intra-arterial hepatic infusion, TACE, especially supplying the gelatin sponge embolization, which can significantly improve the pharmacokinetics parameters,reducing the peripheral drug concentration and untargeted organ toxicity, and increasing the local drug concentration in order to enhance the therapeutic effect. On the dosage form hand, Adriamycin-lipiodol emulsion can significantly reduce the peak concentration, and selectively distributed in liver tumor,achieving the targeted therapy for HCC. While followed by gelatin sponge embolization, the effect will be more obvious.TACE with microcapsule can also obtain obvious pharmacokinetics advantage,which will slowly release and increase the local concentration, prolong the action time and reduce adverse reaction. Peripheral blood drug peek concentration(Cmax) and area under the curve (AUC) of drug-eluting beads(DEB) embolization are significantly lower than Adriamycin-lipiodol emulsion embolization, so the DEB embolization has a better effect than traditional embolization in the treatment of HCC. In a word, to study the effects of medicine method and dosage form on pharmacokinetics plays an important role in improving the therapeutic effect and safety of TACE.