Preiss R, Brovtsyn V K, Perevodchikova N I, Bychkov M B, Hüller H, Belova L A, Michailov P
Department of Clinical Pharmacology, Humboldt University, Berlin, GDR.
Eur J Clin Pharmacol. 1988;34(2):139-44. doi: 10.1007/BF00614550.
The kinetics of platinum in plasma and erythrocytes, and its renal excretion, have been examined in five patients with non-small cell carcinoma of the lung, after treatment with cisplatin 50 mg/m2 (Platidiame) and, three weeks later, a combination of 50 mg/m2 cisplatin and 40 mg/m2 methotrexate. The patients were given 0.9% saline 1 l 1 h prior to drug application. Plasma platinum elimination was biphasic with a short initial phase (t1/2 alpha 10-31 min) and a long beta-phase (t1/2 beta 65-91 h). With the exception of increased AUC values in all five patients 0-8 h after the injection, no significant change in the kinetics of platinum in plasma was found after coadministration of methotrexate. In four of the five patients renal platinum excretion was reduced in the first 6 h after administration of methotrexate. The renal clearance of platinum was 50% lower in those four patients 0-3 h after the injection. With the exception of one patient, no signs of nephrotoxicity were observed after combined drug administration. Other toxic effects were mild and showed no increase after the initial administration of methotrexate.
在五例非小细胞肺癌患者中，研究了顺铂50 mg/m²（Platidiame）治疗后以及三周后50 mg/m²顺铂与40 mg/m²甲氨蝶呤联合治疗后，血浆和红细胞中铂的动力学及其经肾排泄情况。在给药前1小时，给患者输注1升0.9%生理盐水。血浆铂的消除呈双相，初始短相（t1/2α 10 - 31分钟）和长β相（t1/2β 65 - 91小时）。除了所有五例患者注射后0 - 8小时AUC值增加外，甲氨蝶呤联合给药后血浆中铂的动力学未发现显著变化。五例患者中有四例在给予甲氨蝶呤后的前6小时肾铂排泄减少。这四名患者注射后0 - 3小时铂的肾清除率降低了50%。除一名患者外，联合给药后未观察到肾毒性迹象。其他毒性作用较轻，在初次给予甲氨蝶呤后未增加。
