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The effect of kinetic factors on the thermodynamic evaluations of therapeutic chelating agents

Authors
Journal
Inorganica Chimica Acta
0020-1693
Publisher
Elsevier
Publication Date
Volume
138
Issue
1
Identifiers
DOI: 10.1016/s0020-1693(00)81183-4
Disciplines
  • Medicine
  • Pharmacology
  • Physics

Abstract

Abstract The effect of certain kinetic factors on thermodynamic evaluations of several therapeutic chelating agents is examined. This allows the in vivo behavior of these drugs to be understood in more detail. The main kinetic factors examined are: (a) the pharmacokinetics of the chelating agents in vivo; (b) the kinetics by which the toxic metal ions are distributed between the serum and other organs; and (c) the rates of the reactions between the therapeutic chelating agent and the complexes formed by the toxic metal ion with serum constituents. A new parameter is proposed for predicting the efficacy of metal binding in plasma. This takes into account changes in the chelating agent concentration with time. Predictions of the relative efficacy of the therapeutic agents based solely on thermodynamic calculations are shown to provide a useful differential indicator for spontaneous detoxification processes, whereas kinetic factors become more important in delayed treatments or when the chelating agents exhibit similar thermodynamic behavior.

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