Pharmacokinetics of intact cisplatin in plasma. Infusion versus bolus dosing

Abstract

Plasma levels of total platinum, total filterable platinum and intact cisplatin were monitored in 4 patients who received cisplatin in a regimen consisting of 20 mg/m 2 by i.v. bolus followed immediately by 80 mg/m 2 by 6 h infusion. Baseline pharmacokinetic parameters were obtained from a previous study in which 100 mg/m 2 of cisplatin was administered by a single i.v. bolus. These baseline pharmacokinetic parameters were used in an attempt to predict the pharmacokinetic behavior of cisplatin in the present study. The results demonstrated close agreement between observed and predicted plasma level-time profiles and the area under the plasma concentration-time profiles for cisplatin. The ratios of the various platinum species in plasma over the time course of the study were also consistent with those previously reported. These findings suggest that at a dose of 100 mg/m 2, the pharmacokinetics of cisplatin and its conversion to other species in plasma are independent of dosage schedule. Since 100 mg/m 2 is a relatively high dose of cisplatin, it is likely that this approach is applicable to other doses and schedules, and ultimately might prove useful in designing optimum cisplatin dosage regimens.