Cole W C, Wolf W
Chem Biol Interact. 1980 May;30(2):223-35. doi: 10.1016/0009-2797(80)90128-3.
195mPt-cis-Dichlorodiammine platinum(II) (195mPt-cisplatin) binds in vitro essentially irreversibly to bovine serum albumin (BSA) and rat plasma proteins at a 195mPt-cisplatin/protein molar ratio of 1:1 or less. The binding to rat serum proteins shows no apparent specificity, with albumin retaining the greatest fraction of the label (40-55%). The binding is neither instantaneous nor linear with time. Upon intravenous administration to rats of a rat serum protein bound 195mPt-cisplatin, the label remains bound to the proteins while in the blood. The label is cleared from the blood faster than a relatively native 131I-labeled human serum albumin (HSA) and accumulates primarily in the liver. The blood disappearance and organ distribution of the rat serum protein bound 195mPt-cisplatin is consistent with a modified protein. Approx. 11% of the injected dose was excreted via the urine in 24 h in a form which has a different chromatographic mobility than free 195mPt-cisplatin. Since little intact protein is lost in the urine, the excreted label probably represents the product(s) of metabolism of the rat serum bound 195mPt-cisplatin. Due to the apparent irreversibility (both in vivo and in vitro) of the protein/195mPt-cisplatin complex, it is unlikely that the protein bound fraction of the administered 'free' drug will serve as a therapeutically useful 'drug resevoir'.
195mPt-顺式二氯二氨合铂（II）（195mPt-顺铂）在体外以195mPt-顺铂/蛋白质摩尔比为1:1或更低时，基本上不可逆地与牛血清白蛋白（BSA）和大鼠血浆蛋白结合。与大鼠血清蛋白的结合没有明显的特异性，白蛋白保留了最大比例的标记物（40-55%）。这种结合既不是瞬间发生的，也不是随时间呈线性的。给大鼠静脉注射与大鼠血清蛋白结合的195mPt-顺铂后，标记物在血液中时仍与蛋白质结合。该标记物从血液中清除的速度比相对天然的131I标记的人血清白蛋白（HSA）快，并且主要在肝脏中积累。与大鼠血清蛋白结合的195mPt-顺铂的血液消失和器官分布与一种修饰的蛋白质一致。大约11%的注射剂量在24小时内通过尿液以一种色谱迁移率与游离195mPt-顺铂不同的形式排泄。由于尿液中几乎没有完整的蛋白质丢失，排泄的标记物可能代表与大鼠血清结合的195mPt-顺铂的代谢产物。由于蛋白质/195mPt-顺铂复合物在体内和体外都表现出明显的不可逆性，给药的“游离”药物中与蛋白质结合的部分不太可能作为一种有治疗作用的“药物储存库”。
