大剂量顺铂股动脉灌注联合血液透析动物模型的试验研究

目的 研究大剂量顺铂动脉灌注联合血液透析在提高肢体肿瘤化疗药物剂量强度，减少药物在正常组织器官分布方面的作用。方法 体外实验中，将顺铂加入血浆，经血液透析，测定透析前后血浆中及透析液中的铂浓度；体内实验中16只犬随机分为2mg／kg对照(A组)和实验组(B组)，及4mg／kg对照(C组)和实验组(D组)。分别经右股动脉顺铂灌注，实验组右殷静脉插管接血液透析机。采用原子吸收法测定不同时间血液透析机动、静脉端及外周血样、各脏器组织中的铂浓度。结果 在各剂量组中，实验组外周血药浓度—时间曲线下面积(AUC)及外周器官中铂浓度均低于对照组，而灌注化疗肢体局部组织中铂浓度无显差异。D组中灌注化疗肢体局部组织中铂浓度高于B组，而AUC值及外周器官中铂浓度则无显性差异。结论 与普通顺铂股动脉灌注相比，联合血液透斫治疗可以明显降低实验动物外周血药浓度和组织器官药物浓度，在不增加外周药物分布的前提下，有效提高肢体局部用药剂量。

Experimental study on combining femoral artery infusion of high dose cisplatin with hemodialysis in an animal model

Objective To study the effects of increasing dose intensity and reducing systemic drug exposure with combining artery infusion of high dose cisplatin with hemodialysis in the extremity. Methods The capability of a hemo- dialysis dialyzer removes cisplatin from circulating plasma was tested in vitro and compared the extraction of cisplatin to that of creatinine, a molecule of similar size. In vivo, 8 dogs in group A and B were received 2mg/kg cisplatin infusion from right femoral artery and the other 8 dogs in group C and D were received 4mg/kg. In group B and D, the blood from right femoral vein was dialyzed extracorporeally while and after the time of drug perfusion. And animals in group A and C only received cisplatin infusion were chosen as control separately.The platinum concentrations in blood and tissues were tested by flameless atomic absorption spectrophotometry. Results Both the platinum of AUC and the platinum concentra- tion of systemic organs in Group B were significantly lower than that in Group A, but there was no significant difference of tissue platinum concentration in infused extremity between two groups. And the same results were presented in Group D and C. Higher tissue platinum concentration of extremity and same level of AUC and the platinum concentration of sys- temic organs were showen in Group D when compared with Group B. Conclusion These results indicated that combining intra - arterial cisplatin infusion with hemodialysis can produce a significant reduction in systemic drug exposure and may allow dose intensification during intra-arterial chemotherapy for the extremity.