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

作者:Escuder Gilabert Laura; Martinez Gomez Maria Amparo; Villanueva Camanas Rosa Maria; Sagrado Salvador; Medina Hernandez Maria Jose*
来源:Biomedical Chromatography, 2009, 23(3): 225-238.
DOI:10.1002/bmc.1134

摘要

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.

  • 出版日期2009-3