Microseparation techniques for the study of the enantioselectivity of drug-plasma protein binding.
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.
Escuder-Gilabert
Laura
L
Departamento de Química Analítica, Universitat de València, Spain.
Martínez-Gómez
María Amparo
MA
Villanueva-Camañas
Rosa María
RM
Sagrado
Salvador
S
Medina-Hernández
María José
MJ
D000495:Allosteric Site; D001798:Blood Proteins / Q000378:metabolism*; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D019075:Electrophoresis, Capillary; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D013045:Species Specificity; D013237:Stereoisomerism
D001798:Blood Proteins; D004364:Pharmaceutical Preparations