Interaction of the anticoagulant drug warfarin and its metabolites with human plasma albumin
AUTOR(ES)
O'Reilly, Robert A.
RESUMO
The interaction of the anticoagulant drug warfarin and its metabolites with human plasma albumin was studied by equilibrium dialysis. A 20-fold variation of buffer ionic strength (0.017-0.340) caused no significant change in the warfarin association constant. But the binding strength rose significantly as the pH was increased from 6.0 to 9.0 and then declined at pH 10.0. The 6-, 7-, and 8-hydroxywarfarin metabolites showed a 7- to 23-fold reduction in binding strength at pH 10.0. These data indicate that the molecular basis of the interaction is nonelectrostatic and that the introduction of polar hydroxyl groups on the coumarin nucleus by metabolism reduces its hydrophobic binding surface. The interaction was markedly exothermic and showed a positive entropy (increased molecular disorder), which suggests cooperative hydrogen and hydrophobic bonding as the molecular basis for the binding of warfarin to albumin.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=322205Documentos Relacionados
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