PMID: 3746636Apr 1, 1986Paper

Physiological pharmacokinetic modeling of cis-dichlorodiammineplatinum(II) (DDP) in several species

Journal of Pharmacokinetics and Biopharmaceutics
F G KingF F Farris

Abstract

A physiological pharmacokinetic analysis of cis-dichlorodiammineplatinum(II) (DDP) is presented for the rabbit, dog, and human. The results are compared to a previous analysis for the rat. DDP binds irreversibly to low-molecular weight nucleophiles and macromolecules to form mobile and fixed metabolites at rates which are tissue-specific. The rate constant for the formation of fixed metabolite in plasma, determined by in vitro incubation, ranges from 0.004 to 0.008 min-1 in all species. Urinary excretion is the major route of platinum elimination in all species, with a kidney clearance of DDP approximating GFR in all species. Biliary clearance accounts for the elimination of 1-5% of dose and was neglected. The tissue-specific DDP-to-protein binding rates are in the order: kidney/skin/liver/gut/muscle for the beagle dog and rat. The rate constants for the rabbit and mongrel dog are similar, except that the skin and liver are reversed. The binding rate constants for various tissues are similar for all species. The rate constants for release of Pt from macromolecules are similar to protein turnover rate constants and decrease with increasing body weight. Human pharmacokinetic behavior was predicted by estimating human parameters b...Continue Reading

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Citations

Jan 1, 1991·European Journal of Clinical Pharmacology·J F BelliveauP Calabresi
Oct 1, 1988·Toxicology Letters·F F FarrisF G King
Sep 1, 1996·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·I Mahmood, J D Balian
Oct 7, 2015·Journal of Veterinary Pharmacology and Therapeutics·S AchantaL K Maxwell
Feb 1, 1992·Journal of Pharmacokinetics and Biopharmaceutics·F G King, R L Dedrick
Dec 18, 2009·Toxicology Letters·A L PoirrierB Malgrange
Apr 1, 1995·Journal of Pharmacokinetics and Biopharmaceutics·S B CharnickH Sato
Jun 19, 2008·Journal of Clinical Pharmacology·Kosalaram GotetiC Edwin Garner
Nov 17, 1999·Journal of Pharmaceutical Sciences·I Mahmood

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