Perera A, Jackson H, Sharma H L, McAuliffe C A, Fox B W
Department of Chemistry, University of Manchester Institute of Science and Technology, UK.
Chem Biol Interact. 1992 Dec;85(2-3):199-213. doi: 10.1016/0009-2797(92)90062-p.
Plasma protein binding of 195mPt-labelled cisplatin, carboplatin and iproplatin has been studied in vivo in rat and in vitro in mouse, using both electrophoresis and trichloroacetic acid precipitation. After intravenous injection plasma clearance rates were biphasic for all 3 compounds, (t1/2 alpha, 13-17 min) but cisplatin was retained thereafter longer than the others. By 5 min, gel electrophoresis showed protein labelling with all 3 drugs but none involved low mol.wt. proteins (< 16 kDa). At 2 h a notable proportion of the protein bound platinum was associated with the latter components. There was a general resemblance between the distribution patterns of cisplatin and carboplatin whereas iproplatin showed a persistent retention of the label with time to higher mol. wt. proteins. From in vitro incubation with mouse plasma, rates of interaction respectively were cisplatin t1/2 alpha, 35 min, beta 8 h, carboplatin t1/2, 44 h and iproplatin t1/2, 104 h. By electrophoresis the protein bound fraction pattern (1 h) was again similar for cisplatin and carboplatin with virtually no binding to low mol. wt. proteins. After 24 h these were now involved to a high degree (40%). Iproplatin showed relatively marked binding to proteins of higher mol. wt. but no transfer with time to the low mol. wt. protein zone. A possible explanation is the need for in vivo metabolism for this compound as manifest in the rat. It is suggested that the significance of interaction with low mol. wt. proteins merits further investigation in relation to the antitumour and toxicological actions of these drugs.
利用电泳和三氯乙酸沉淀法，对195mPt标记的顺铂、卡铂和异丙铂在大鼠体内的血浆蛋白结合情况以及在小鼠体外的血浆蛋白结合情况进行了研究。静脉注射后，所有3种化合物的血浆清除率均呈双相性（t1/2α，13 - 17分钟），但顺铂此后的保留时间比其他化合物更长。5分钟时，凝胶电泳显示所有3种药物均有蛋白标记，但均未涉及低分子量蛋白（<16 kDa）。2小时时，与蛋白结合的铂有相当一部分与后一种成分相关。顺铂和卡铂的分布模式总体相似，而异丙铂随着时间的推移，标记物持续保留在较高分子量的蛋白质上。从小鼠血浆体外孵育实验来看，相互作用速率分别为：顺铂t1/2α，35分钟，β8小时；卡铂t1/2，44小时；异丙铂t1/2，104小时。通过电泳，顺铂和卡铂的蛋白结合部分模式（1小时）再次相似，几乎没有与低分子量蛋白结合。24小时后，低分子量蛋白现在高度参与结合（40%）。异丙铂显示出与较高分子量蛋白有相对明显的结合，但没有随时间转移到低分子量蛋白区域。一种可能的解释是，该化合物在大鼠体内表现出需要体内代谢。建议就这些药物的抗肿瘤和毒理学作用而言，与低分子量蛋白相互作用的意义值得进一步研究。
