Pharmacokinetics of platinum in cancer patients treated with carboplatin in combination with high-dose methotrexate.

Abstract

The pharmacokinetics of platinum was investigated in 10 cancer patients treated with a 1-hr infusion of 300 mg/m2 of carboplatin which was given 2-4 days after the administration of 100 mg/kg (20-mg/kg bolus and 80-mg/kg intravenous infusion) of methotrexate. Platinum was analyzed in the samples by flameless atomic absorption spectrophotometry. The concentration vs time data for total platinum in plasma followed a two-compartment model and the mean (and SE) values for beta, TBC, Vc, and RC were 0.0827 (0.22) hr-1, 2.355 (0.252) liters/hr . m2, 10.74 (0.62) liters/m2, and 2.405 (0.228) liters/hr . m2, respectively. There was no significant change in the creatinine clearance or TBC with repeated treatment. The ultrafilterable platinum which was measured in the plasma of two patients constituted 82 and 11.3% of the total platinum at 1 and 24 hr, respectively, and the data conformed to the one-compartment model. The mean (SE) values for t 1/2, TBC, and Vd for free platinum were 1.844 (0.208) hr, 4.583 (1.059) liters/hr . m2, and 11.88 (1.45) liters/m2, respectively. The above data are in good agreement with those reported earlier for platinum following the administration of carboplatin as a single agent. These results suggest that high-dose methotrexate therapy, when administered 2-4 days before carboplatin, does not affect the pharmacokinetics of platinum in the plasma.