CISPLATIN PHARMACOKINETICS USING A 5-DAY SCHEDULE DURING REPEATED COURSES OF CHEMOTHERAPY IN GERM-CELL TUMORS

Total and ultrafilterable platinum (Pt) disposition was investigated during 49 courses of chemotherapy in 13 patients with germ cell tumor treated with cisplatin (DDP), 20 mg/m(2)/day on 5 consecutive days. The following pharmacokinetic parameters were analyzed: distribution (t(1/2)alpha) and elimination (t(1/2)beta) half-lives, total body clearance (Cl-T), renal clearance (Cl-R), and areas under the concentration versus time curve (AUCs). Blood samples were collected immediately before and after DDP infusion (Day 1 through Day 5); in addition, on Day 5, samples were collected at 0.25, 0.5, 1, 8, 24, and 48 h after DDP infusion. Urine was collected during each day of treatment and up to 48 h after the last DDP dose. During each chemotherapy cycle plasma levels of total and ultrafilterable Pt progressively increased from the first to the last day of treatment. At the first cycle, total Pt concentrations ranged from 0.67 to 1.46 mu g/ml (mean increase, 118%), and those of ultrafilterable Pt from 0.117 to 0.205 mu g/ml (mean increase, 75%). Mean +/- SD total Pt plasma levels immediately postinfusion increased from 0.67 +/- 0.20 mu g/ml at the first cycle (first day of therapy) to 1.13 +/- 0.21 mu g/ml at the same time point at the fourth cycle. Mean total Pt peak levels were reached at the end of infusion on the last day of each cycle, and increased from 1.46 +/- 0.29 mu g/ml (first cycle) to 1.89 +/- 0.40 mu g/ml (fourth cycle). Total Pt was detectable in plasma before the beginning of all cycles following the first. As a result, AUC significantly increased and Cl-R significantly decreased. However, this change was no longer evident when calculations were made taking into account the pretreatment values of total Pt. Plasma concentrations of ultrafilterable Pt did not show any significant change between the first and subsequent cycles; nor was there any significant modification in the pharmacokinetic parameters studied.