Pharmacokinetics of non-protein-bound platinum species following administration of cis-dichlorodiammineplatinum(II).
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.
D001202:Ascitic Fluid / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008353:Mannitol / Q000008:administration & dosage; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011485:Protein Binding
D008353:Mannitol; D002945:Cisplatin