Elferink F, van der Vijgh W J, Klein I, Pinedo H M
Clin Chem. 1986 Apr;32(4):641-5.
Toxicity of cisplatin can be decreased by concomitant administration of sodium thiosulfate, which perhaps chemically inactivates this platinum compound. We studied the disappearance of cisplatin and carboplatin in aqueous solutions of thiosulfate at 37 degrees C by means of liquid chromatography. At initial concentrations that were similar to therapeutic concentrations in plasma, both drugs disappeared, with half-lives of 66 and 537 min for cisplatin and carboplatin, respectively. At higher thiosulfate concentrations, as found in urine, the respective half-lives were 3.7 and 33.8 min. These values suggest that direct chemical interaction in the plasma compartment has limited therapeutic consequences, whereas the anti-toxic effect of thiosulfate might be explained by the rapid inactivation of cisplatin in the kidneys. Reaction products of cisplatin and thiosulfate bound instantaneously and mainly reversibly to plasma proteins. Protein-bound cisplatin was not released by added thiosulfate--which may explain why thiosulfate, to be effective, must be given in advance of and during cisplatin administration.
同时给予硫代硫酸钠可降低顺铂的毒性，这可能是通过化学方法使这种铂化合物失活。我们通过液相色谱法研究了37℃时硫代硫酸盐水溶液中顺铂和卡铂的消失情况。在与血浆中治疗浓度相似的初始浓度下，两种药物均消失，顺铂和卡铂的半衰期分别为66分钟和537分钟。在尿液中发现的较高硫代硫酸盐浓度下，各自的半衰期分别为3.7分钟和33.8分钟。这些值表明，血浆隔室中的直接化学相互作用对治疗效果的影响有限，而硫代硫酸盐的抗毒作用可能是由于顺铂在肾脏中迅速失活所致。顺铂和硫代硫酸盐的反应产物立即且主要以可逆方式与血浆蛋白结合。添加硫代硫酸盐不会释放与蛋白结合的顺铂，这也许可以解释为什么硫代硫酸盐要有效就必须在顺铂给药之前及给药期间给予。
