Disposition of anticancer drugs after bolus arterial administration in a tissue-isolated tumor perfusion system.
Disposition of anticancer drugs after bolus arterial administration in a tissue-isolated tumor perfusion system.
复制标题
在组织隔离的肿瘤灌注系统中经动脉推注给药后抗癌药物的处置。
作者：
K. Ohkouchi;H. Imoto;Y. Takakura;M. Hashida;H. Sezaki
采用原位单向血管灌注技术，在步行者256只荷瘤大鼠中研究了各种抗癌药物在组织分离肿瘤制剂中的处置特征。三种抗癌药物，5-氟尿嘧啶，丝裂霉素C，阿霉素，和丝裂霉素C的两个亲脂性前体药物进行了测试，在肿瘤制备灌注台氏液含有4.7%的牛血清白蛋白。采用统计矩理论分析受试药物动脉推注后的流出液浓度-时间曲线。在每个肿瘤制备物中，药物的注射与血管参照物（Evans蓝标记的牛血清白蛋白）的注射配对，并且药物的处置参数与血管参照物的处置参数校正。根据血管参比物质的平均通过时间值，计算肿瘤制剂的平均血管体积为0.063 ml/g，其随着肿瘤生长而减小。所有药物均显示出显著的肿瘤组织提取，这取决于它们的理化性质。供试药物的分布容积为血管容积的1.53 ~ 3.33倍。随着药物亲脂性的增加，计算的蛋白质未结合部分的固有清除率值增加。在丝裂霉素C的亲脂性前药中观察到肿瘤摄取的潜在增加。因此，本实验系统是有用的，用于分析药物在肿瘤组织中的处置。
Disposition characteristics of various anticancer drugs in a tissue-isolated tumor preparation were studied in Walker 256 carcinosarcoma-bearing rats using an in situ single-pass vascular perfusion technique. Three anticancer drugs, 5-fluorouracil, mitomycin C, and Adriamycin, and two lipophilic prodrugs of mitomycin C were tested in the tumor preparation perfused with Tyrode's solution containing 4.7% bovine serum albumin. After bolus arterial injection of test drugs, their outflow concentration-time curves were analyzed based on statistical moment theory. In each tumor preparation, the injection of drug was paired with that of vascular reference substance, Evans' blue-labeled bovine serum albumin, and disposition parameters of the drug were corrected with those of vascular reference substance. From the mean transit time values of vascular reference substance, the average vascular volume of the tumor preparation was calculated to be 0.063 ml/g, which decreased with tumor growth. All drugs showed significant extraction by the tumor tissue, depending on their physicochemical properties. Distribution volumes of tested drugs were from 1.53 to 3.33 times larger than the vascular volume. Calculated intrinsic clearance values for the protein-unbound fractions increased as the lipophilicity of the drug increased. The potential increase in tumor uptake was observed in lipophilic prodrugs of mitomycin C. The present experimental system is thus suggested to be useful for analyzing drug disposition in tumor tissue.
高血糖期间组织分离的 Walker 256 癌的血流和静脉 pH 值。
影响因子：
11.2
作者：
Sevick,EM;Jain,RK
通讯作者：
Jain,RK