Pharmacokinetics of free and total platinum species after rapid and prolonged infusions of cisplatin.

Pharmacokinetic studies were performed in 51 patients who received cisplatin infusions. Two treatment regimens (single-day or daily for 5 days) and three infusion schedules (for 4 to 15 minutes, 2 to 3 hours, or 24 hours) were used. The daily dose of cisplatin varied from 20 to 120 mg/m2. The kinetics of total platinum studied up to day 5 revealed differences only during the initial period after the infusion. Peak levels were both dose and schedule dependent and initial t1/2 values in the decay curves were only schedule dependent (mean values: 13 minutes for rapid infusions, 40.3 minutes for 2 to 3-hour infusions, and 220.5 minutes for 24-hour infusion). The t1/2 values between days 1 and 5 were neither dose nor schedule dependent (mean 5.0 to 7.3 days). Concentrations of free platinum declined biexponentially after the rapid and 2 to 3-hour infusions, but they declined monoexponentially after 24-hour infusions. Final t1/2 values ranged from 26.0 to 78.8 minutes. In patients with normal renal and hepatic function, the free platinum AUC was identical for cisplatin infusions of different duration when equal doses were given. Free platinum clearance correlated with creatinine clearance (P = 0.017). The uptake of platinum in red blood cells was rapid, and peak concentrations correlated with the free platinum AUC (P = 0.0006), independent of the infusion schedule. The decay of platinum levels in red blood cells was biphasic. The mean terminal t1/2 for the interval between days 5 and 15 was 29.8 days. This suggests a breakdown of red blood cells that results from cisplatin dosing.