Pharmacokinetics of cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum IV (CHIP) in patients with advanced cancer |
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Authors: | L. Pendyala W. Greco J. W. Cowens S. Madajewicz P. J. Creaven |
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Affiliation: | (1) Department of Clinical Pharmacology and Therapeutics, Roswell Park Memorial Institute, New York State Department of Health, 14263 Buffalo, NY, USA;(2) Computer Center, Roswell Park Memorial Institute, New York State Department of Health, 14263 Buffalo, NY, USA;(3) Department of Experimental Therapeutics, Roswell Park Memorial Institute, New York State Department of Health, 14263 Buffalo, NY, USA |
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Abstract: | Summary 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 -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. |
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