Effect of methotrexate on the pharmacokinetics and renal excretion of cisplatin

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.