Microseparation techniques for the study of the enantioselectivity of drug–plasma protein binding

Authors

  • Laura Escuder-Gilabert,

    1. Departamento de Química Analítica, Universitat de València, C/ Vicente Andrés Estellés s/n, 46100-Burjassot, Valencia, Spain
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  • María Amparo Martínez-Gómez,

    1. Departamento de Química Analítica, Universitat de València, C/ Vicente Andrés Estellés s/n, 46100-Burjassot, Valencia, Spain
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  • Rosa María Villanueva-Camañas,

    1. Departamento de Química Analítica, Universitat de València, C/ Vicente Andrés Estellés s/n, 46100-Burjassot, Valencia, Spain
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  • Salvador Sagrado,

    1. Departamento de Química Analítica, Universitat de València, C/ Vicente Andrés Estellés s/n, 46100-Burjassot, Valencia, Spain
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  • María José Medina-Hernández

    Corresponding author
    1. Departamento de Química Analítica, Universitat de València, C/ Vicente Andrés Estellés s/n, 46100-Burjassot, Valencia, Spain
    • Departamento de Química Analítica, Universitat de València, C/Vicente Andrés Estellés s/n, 46100-Burjassot, Valencia, Spain.
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Abstract

Stereoselectivity in protein binding can have a significant effect on the pharmacokinetic and pharmacodynamic properties of chiral drugs. The investigation of enantioselectivity of drugs in their binding with human plasma proteins and the identification of the molecular mechanisms involved in the stereodiscrimination by the proteins represent a great challenge for clinical pharmacology. In this review, the separation techniques used for enantioselective protein binding experiments are described and compared. An overview of studies on enantiomer–protein interactions, enantiomer–enantiomer interactions as well as chiral drug–drug interactions, including allosteric effects, is presented. The contribution of individual plasma proteins to the overall enantioselective binding and the animal species variability in drug–plasma protein binding stereoselectivity are reviewed. Copyright © 2008 John Wiley & Sons, Ltd.

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