顺铂脂质体在顺铂耐药和顺铂敏感癌动物体内的生物分布分析。
Biodistribution analysis of cisplatin in liposomal form in animals with cisplatin-resistant and cisplatin-sensitive carcinoma.
作者信息
Nosko M M, Pivnyuk V M, Solyanik G I, Kulik G I, Todor I N, Momot V Ya, Melnikov O R, Ponomareva O V, Chekhun V F
机构信息
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
出版信息
Exp Oncol. 2010 Mar;32(1):40-3.
AIM
To analyze the relation between pharmacokinetics of cisplatin in liposomal form and antitumor efficacy toward cisplatin-resistant and cisplatin-sensitive variants of Guerin carcinoma.
METHODS
Concentration of platinum was measured by atomic absorption spectrophotometry (C115M1 "Selmi", Ukraine). Elimination constant was calculated based on the dynamics of cisplatin concentration in time period between 1 h to 24 h using nonlinear regression analysis. Area under curve (AUC24) was calculated by the trapezium method.
RESULTS
It was shown that for liposomal form of cisplatin (LCp) AUC24 in tumor practically didn't depend on the level of the tumor sensitivity, while in animals with the resistant variant (CpRGC), AUC24 for free cisplatin (FCp) decreased by 70% less (p < 0.001) as compared to the sensitive tumor strain (CpSGC). Significant decrease of elimination constant of LCp compared to FCp in blood serum of rats bearing either CpRGC or CpSGC tumors favors cisplatin accumulation in tumor tissues with low vascularization level. The dynamics of cisplatin concentration in CpRGC variant was characterized by 90% higher level in 24 h after administration of LCp as compared to FCp (p < 0.05). This fact may explain increased antitumor efficacy of LCp compared to FCp toward CpRGC variant. In the study of kidney function, AUC24 index for LCp was by 68.6% (p < 0.01) and 50.7% (p < 0.05) lower than AUC24 index for FCp in rats with CpRGC and CpSGC variants, respectively. No significant differences have been found in biodistribution of cisplatin in both pharmaceutical forms in liver and lung in CpRGC- or CpSGC-bearing rats.
CONCLUSION
The results suggest that cisplatin in liposomal form possesses higher specificity of antitumor action than free cisplatin.
目的
分析脂质体形式顺铂的药代动力学与对顺铂耐药和敏感的艾氏腹水癌变体的抗肿瘤疗效之间的关系。
方法
采用原子吸收分光光度法（乌克兰的C115M1“塞尔米”）测定铂浓度。使用非线性回归分析，根据顺铂浓度在1小时至24小时时间段内的动态变化计算消除常数。采用梯形法计算曲线下面积（AUC24）。
结果
结果表明，对于脂质体形式的顺铂（LCp），肿瘤中的AUC24实际上不依赖于肿瘤敏感性水平，而在携带耐药变体（CpRGC）的动物中，游离顺铂（FCp）的AUC24比敏感肿瘤株（CpSGC）降低了70%以上（p<0.001）。在携带CpRGC或CpSGC肿瘤的大鼠血清中，LCp的消除常数与FCp相比显著降低，这有利于顺铂在血管化程度低的肿瘤组织中蓄积。与FCp相比，在给予LCp后24小时，CpRGC变体中顺铂浓度的动态变化特征是水平高90%（p<0.05）。这一事实可能解释了与FCp相比，LCp对CpRGC变体的抗肿瘤疗效增加。在肾功能研究中，在携带CpRGC和CpSGC变体的大鼠中，LCp的AUC24指数分别比FCp的AUC24指数低68.6%（p<0.01）和50.7%（p<0.05）。在携带CpRGC或CpSGC的大鼠中，两种剂型的顺铂在肝脏和肺中的生物分布未发现显著差异。
结论
结果表明，脂质体形式的顺铂比游离顺铂具有更高的抗肿瘤作用特异性。
Zotero 插件