长春新碱脂质体的药代动力学及其抗肿瘤作用

›› 2007, Vol. 27 ›› Issue (1): 15-19.

长春新碱脂质体的药代动力学及其抗肿瘤作用

1.上海医药工业研究院药理室,上海 200437；2.上海复旦张江生物医药股份有限公司,上海 201203

收稿日期:2006-09-11 出版日期:2007-01-31 发布日期:2007-01-31

Study on Phamacodynamic Properties of L-VCR and Its Anti-tumor Effect

1. Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437,China; 2. Shanghai Fudan-zhangjiang Bio-Pharmaceutical Co.,Ltd, Shanghai 201203, China

Received:2006-09-11 Online:2007-01-31 Published:2007-01-31

摘要/Abstract

摘要： 目的进行脂质体长春新碱（Liposome Vincristine，L-VCR）的动物体内药代学研究、体内抗肿瘤药效学研究以及毒理学研究，探讨L-VCR的作用特点及其可能的作用机制.方法 Wistar大鼠接种Walker256肿瘤，用高效液相色谱-紫外检测法（HPLC-UV），测定其体内以及肿瘤内的血药浓度，用药动学计算软件拟合处理得药动学参数；小鼠接种B16黑色素瘤，静脉给予L-VCR，计算其肿瘤抑制率以及去瘤体重测定L-VCR小鼠的LD50.结果与游离长春新碱（Free Vincristine，F-VCR）相比，L-VCR血浆以及肿瘤内浓度增高，维持时间明显延长，AUC_0-t增加约121倍；L-VCR能明显减轻小鼠B16黑色素瘤模型的瘤体重量，并呈现一定的量效关系；L-VCR小鼠的LD50明显高于游离药物.结论 L-VCR可显著延长VCR半衰期，增大药时曲线下面积，药效明显高于F-VCR，且毒性明显降低.其作用可能是通过脂质体包裹，增加肿瘤中的药物量，延长VCR的作用时间，药物释放缓慢，从而减轻VCR的毒性而达到的。

关键词: 长春新碱脂质体, HPLC-UV, 药代动力学, 药效学

Abstract: Objectives To analyze the pharmacodynamic properties of liposome Vincristine (L-VCR), its pharmacological effects against tumor and toxicology. The characteristics of L-VCR and the possible mechanism of its actions were discussed. Methods Wistar rats were inoculated with Walker256 tumor. Blood drug level was analyzed by HPLC and pharmacodynamic parameters were calculated using computer software. Mice were inoculated with B16 melanoma and L-VCR was given i.v. Tumor inhibi-toiy rate and non-tumor body weight was calculated. The LD50 for L-VCR was determined in both rats and mice. Results Compared with Free Vincristine (F-VCR), the plasma and tumor level of L-VCR was higher and sustained significantly longer. Its AUCQ25-t was increased about 121 times after treatment. L-VCR at 2 — 0.5 mg/kg dosage could significantly reduce the weight of the tumor mass in all three cases mentioned above and certain does-effect correlation could be observed. Compared with that of F-VCR, the LD50 of L-VCR was significantly higher in animals. Conclusion L-VCR could significantly extend the half-life of VCR and increase the AUC. Its effects on transplantable tumors was significantly stronger compared to that of F-VCR while its toxicity was significantly lower. The effective period of VCR was prolonged due to the coating of liposome and its level in tumor was increased. The drug was released slower and its toxicity was therefore reduced.

Key words: L-VCR, HPLC-UV, Pharmacodynamics, Pharmacology, Toxicology

王小晨1，王向伟1，秦燕1，徐智儒1，王光凤1，来庆勤1，杨正茂2，刘全海1. 长春新碱脂质体的药代动力学及其抗肿瘤作用[J]. , 2007, 27(1): 15-19.

WANG Xiao-chen1;WANG Xiang-wei1;QIN Yan1;XU Zhi-ru1;WANG Guang-feng1;LAI Qing-qin1;YANG Zhen-mao2;LIU Quan-hai1. Study on Phamacodynamic Properties of L-VCR and Its Anti-tumor Effect[J]. , 2007, 27(1): 15-19.

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