Pharmacokinetics of cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum IV (CHIP) in patients with advanced cancer.
The pharmacokinetics of a second-generation platinum (Pt) analog cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum IV (CHIP) have been studied in 12 patients at doses from 20 to 350 mg/m2. Three Pt species have been measured: total Pt and non-protein-bound Pt by atomic absorption spectrophotometry, and unchanged CHIP by separation on high-performance liquid chromatography followed by atomic absorption spectrophotometry. Plasma decay of total Pt was biexponential at all doses with a beta-phase half-life of 32.1-124 h. Plasma decay of filterable Pt was monoexponential at low doses but biexponential at high doses, with a terminal-phase half-life of 17.8-54.6 h. Plasma decay of unchanged CHIP was monoexponential at all doses, with a half-life of 0.64-1.27 h. Excretion of Pt after CHIP was rapid up to 10 h after the end of infusion and then slow. The total recovery of Pt was 15%-61% of the dose at 24 h in 19 patients. The data indicated that essentially all plasma Pt after 12 h is in the form of metabolites, most of which are protein-bound. The most striking difference between CHIP and reported data for cisplatin is the biexponential decay of non-protein-bound Pt.
D000970:Antineoplastic Agents / Q000378:metabolism*; D004341:Drug Evaluation; D006801:Humans; D007700:Kinetics; D008433:Mathematics; D009369:Neoplasms / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000378:metabolism*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C023359:iproplatin