Leone R, Fracasso M E, Soresi E, Cimino G, Tedeschi M, Castoldi D, Monzani V, Colombi L, Usari T, Bernareggi A
Institute of Pharmacology, Policlinico Borgo Roma, Verona, Italy.
Cancer Chemother Pharmacol. 1992;29(5):385-90. doi: 10.1007/BF00686008.
The kinetics of platinum (Pt) was studied in 12 patients suffering from non-small-cell lung cancer or pleural mesothelioma. Each subject received an infusion of cisplatin (CDDP, 80 mg/m2), and six patients were pretreated with glutathione (GSH, 2.5 g given i.v.) at 15 min prior to the cisplatin infusion. After a 3- to 4-week interval, all patients were given a second course of treatment on the same schedule. A biexponential model was fitted to plasma concentrations of total and ultrafilterable Pt. The excretion of Pt in urine was evaluated during the first 48 h after the CDDP infusion. Following the administration of CDDP alone or with GSH pretreatment, the pharmacokinetic parameters of Pt did not significantly differ between the treatments. Also, the unbound fraction determined at each sampling time did not vary significantly between the treatments. However, it is noteworthy that the mean values obtained for the terminal half-life, the volume of distribution, the renal clearance, the percentage of the dose excreted in the urine, and the mean residence time of total Pt were higher in patients who had been pretreated with GSH, suggesting that GSH might increase both the rate of Pt elimination and the extent of Pt distribution and, as a consequence of the latter, might prolong the residence time of Pt in the body. In addition, the unbound fraction of Pt from the 4th to the 48th was higher following the first dose of CDDP+GSH than after treatment with CDDP alone. Because of the rather high variability in the values of the parameters obtained, further work is planned using a larger number of patients.
对12例非小细胞肺癌或胸膜间皮瘤患者的铂（Pt）动力学进行了研究。每位受试者接受顺铂（CDDP，80mg/m²）静脉输注，其中6例患者在顺铂输注前15分钟静脉注射谷胱甘肽（GSH，2.5g）进行预处理。经过3至4周的间隔后，所有患者按照相同方案接受第二个疗程的治疗。对总铂和超滤铂的血浆浓度拟合双指数模型。在CDDP输注后的头48小时内评估尿中Pt的排泄情况。单独给予CDDP或进行GSH预处理后，各治疗组之间Pt的药代动力学参数无显著差异。此外，各采样时间点测定的游离分数在各治疗组之间也无显著变化。然而，值得注意的是，接受GSH预处理的患者中，总Pt的终末半衰期、分布容积、肾清除率、尿中排泄剂量的百分比以及平均驻留时间的平均值较高，这表明GSH可能会增加Pt的消除速率和分布范围，并且由于后者，可能会延长Pt在体内的驻留时间。此外，首次给予CDDP+GSH后，第4小时至第48小时Pt的游离分数高于单独使用CDDP治疗后。由于所获得参数值的变异性相当高，计划使用更多患者进行进一步研究。
