肝硬化时开普拓用药影响的实验研究

Experimental study on the influence of liver cirrhosis in irinotecan administration

目的探讨肝硬化对开普拓代谢、副作用及抗肿瘤作用的影响。方法实验分4组,A组为正常对照组(开普拓给药100mg/kg);B、C、D组为肝硬化组(开普拓给药分别为100、60、30mg/kg)。用高效液相色谱法检测给药后开普拓及SN-38血药浓度变化,观察副作用及抗肿瘤作用。结果肝硬化时小鼠对开普拓及SN-38的代谢均减弱,尤其以对SN-38的影响为明显。开普拓给药后A、B、C、D组体重减少最大值(g)分别为7.3±3.0,12.7±2.3,6.3±5.6,3.2±1.7,B组与各组间差异有显著意义。白细胞减少最大值(个/mm3)分别为655±100,1695±420,800±145,240±230,除A组与C组间外,其余各组间差异有显著意义。治疗后肿瘤直径(cm)分别为1.7±0.3,1.1±0.4,1.6±0.3,1.9±0.1,B组与各组间差异有显著意义。结论小鼠肝硬化时开普拓代谢减慢,副作用明显增加,同时抗肿瘤作用也可能增强。

Objective To investigate the influence of liver cirrhosis on the metabolism, side effects, and anti-tumor effect of irinotecan. Methods Mice were randomly divided into 4 groups： group A was normal control group（irinotecan was aderministered 100mg/kg）; group B, C, and D was cirrhosis group （irinotecan was aderministered 100, 60, 30mg/kg, respectively）. The change of blood drug concentration of irinotecan and SN-38 were tested by high-performance liquid chromatography. The side effects and anti-tumor effect of irinotecan were observed. Results Metabolism of irinotecan and SN-38 in mice were decreased when liver cirrhosis. Metabolism of SN-38 was influenced more obviously. The biggest value of body weight reduction in group A, B, C, D were 7.3±3.0,12.7±2.3,6.3±5.6,3.2±1.7, respectively. There was significant difference between group B and the other groups. The biggest value of the reduction of white blood cell in group A,B,C,D were 655±100,1695±420,800±145,240±230, respectively. There was significant difference between all groups except group A and C. The diameter of tumor after therapy in group A,B,C,D were 1.7±0.3,1.1±0.4,1.6±0.3,1.9±0.1,respectively. There was significant difference between group B and the other groups. Conclusion The metabolism of irinotecan is decreased,but side effects and anti-tumor effect are increased when CTP-11 is applied in cirrhotic mice.