肝硬化对开普拓用药影响的实验研究

Experimental Study of the Influence of Cirrhosis on 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。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 cirrhosis on the metabolism, side effect, 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 was observed.Results Metabolism of irinotecan and SN-38 in mice decreased when cirrhosis. Metabolism of SN-38 was influenced more obviously. The lowest value of body weight reduction in group A, B, C, D is 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 is 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 is 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 decreased with side effects and anti-tumor effect increased when cirrhosis.