Microseparation techniques for the study of the enantioselectivity of drug–plasma protein binding
Article first published online: 17 NOV 2008
Copyright © 2008 John Wiley & Sons, Ltd.
Volume 23, Issue 3, pages 225–238, March 2009
How to Cite
Escuder-Gilabert, L., Martínez-Gómez, M. A., Villanueva-Camañas, R. M., Sagrado, S. and Medina-Hernández, M. J. (2009), Microseparation techniques for the study of the enantioselectivity of drug–plasma protein binding. Biomed. Chromatogr., 23: 225–238. doi: 10.1002/bmc.1134
- Issue published online: 9 FEB 2009
- Article first published online: 17 NOV 2008
- Manuscript Accepted: 28 JUL 2008
- Manuscript Revised: 25 JUL 2008
- Manuscript Received: 14 JUL 2008
- Spanish Ministry of Science and Technology.
- European Regional Development Fund. Grant Number: SAF2005-01435
- Generalitat Valenciana. Grant Number: POSTD/2007/062
- stereoselective drug–plasma protein binding;
- separation techniques;
- enantiomer–enantiomer interactions;
- allosteric effects;
- interspecies effect
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.