Pharmacokinetics of non-protein-bound platinum species following administration of cis-dichlorodiammineplatinum(II)

Abstract

The pharmacokinetics of non-protein-bound platinum species derived from cis-dichlorodiammineplatinum(II) (cis-platinum) was studied under a variety of dosing conditions. Following rapid infusions (15-minute) of cis-platinum at 100 mg/m2, the unbound drug declined in a biphasic mode with a mean terminal half-life of 48 minutes. The mean beta-phase half-life after a 6-hour infusion of the same dose of cis-platinum was 26 minutes. Urinary excretion of filterable platinum was substantially greater after a 6-hour infusion than after a 15-minute injection. Concomitant administration of mannitol appeared to result in higher peak plasma concentrations and decreased urinary excretion of unbound platinum species but did not alter the terminal half-life. Renal impairment was associated with extremely high plasma levels of filterable platinum but did not affect other pharmacokinetic parameters. Preliminary data on the distribution of cis-platinum to ascitic fluid are also presented.