Gandara D R, Perez E A, Denham A, Wiebe V J, DeGregorio M W
Hematology/Oncology Division, University of California, Davis.
Cancer Chemother Pharmacol. 1989;24(2):135-6. doi: 10.1007/BF00263136.
Plasma cisplatin pharmacokinetics were determined in 6 patients enrolled in a phase I trial of combined high-dose cisplatin and Interleukin-2 (IL-2) therapy. Cisplatin (100 mg/m2) was given in 3% saline as a 3-h infusion on days 1 and 8 of each 28-day cycle; IL-2(2-4 x 10(6) units/m2) was given as an i.v. bolus on days 15-19 in a dose escalation trial. Peak total and ultrafiltrate plasma platinum concentrations were 1.15 and 0.172 micrograms/ml for cycle 1 and 1.2 and 0.124 micrograms/ml for cycle 3, respectively. The AUCs for total and ultrafiltrate plasma platinum were 7.33 and 0.965 micrograms/ml per hour for cycle 1 and 8.48 and 0.924 micrograms/ml per hour for cycle 3, respectively. Total body clearances for total and ultrafiltrate platinum were 0.051 and 0.525 ml/h for cycle 1 and 0.042 and 0.443 ml/h for cycle 3, respectively. These data demonstrate no significant effects of IL-2 on the plasma pharmacokinetics of cisplatin in the dose schedule given and support the feasibility of this combined modality therapy.
在一项高剂量顺铂与白细胞介素-2（IL-2）联合治疗的I期试验中，对6名患者测定了血浆顺铂的药代动力学。在每28天周期的第1天和第8天，以3%盐水将顺铂（100mg/m²）作为3小时输注给予；在剂量递增试验中，于第15 - 19天以静脉推注方式给予IL-2（2 - 4×10⁶单位/m²）。第1周期的血浆总铂和超滤铂峰值浓度分别为1.15和0.172μg/ml，第3周期分别为1.2和0.124μg/ml。第1周期的血浆总铂和超滤铂的AUC分别为7.33和0.965μg/ml·小时，第3周期分别为8.48和0.924μg/ml·小时。第1周期总铂和超滤铂的全身清除率分别为0.051和0.525ml/h，第3周期分别为0.042和0.443ml/h。这些数据表明，在所给剂量方案中，IL-2对顺铂的血浆药代动力学无显著影响，并支持这种联合治疗方式的可行性。
