title: Stereoselective plasma protein binding of amlodipine.
abstract: The binding of the (R)- and (S)-enantiomers of amlodipine to bovine serum albumin (BSA), human serum albumin (HSA), alpha(1)-acid glycoprotein (AGP), and human plasma (HP) was studied by equilibrium dialysis over the concentration range of 75-200 microM at a protein concentration of 150 microM. Unbound drug concentrations were determined by enantioselective capillary electrophoresis using 50 mM phosphate buffer, pH 2.5, containing 18 mM alpha-cyclodextrin as background electrolyte. Saturation of the protein binding sites was not observed over the concentration range tested. Upon application of racemic amlodipine besylate, (S)-amlodipine was bound to a higher extend by HSA and HP compared with (R)-amlodipine, whereas the opposite binding of the enantiomers was observed for BSA and AGP. Scatchard analysis was used to illustrate the different binding affinities of amlodipine besylate enantiomers to BSA, HSA and AGP.
authors.affiliation: Department of Pharmaceutical Chemistry, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Maddi
authors.forename: Madhusudan Rao
authors.initials: MR
authors.lastname: Yamsani
authors.forename: Andreas
authors.initials: A
authors.lastname: Seeling
authors.forename: Gerhard K E
authors.initials: GK
authors.lastname: Scriba
mesh_terms: D000418:Albumins / Q000378:metabolism; D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects*; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism*; D002417:Cattle; D006801:Humans; D007700:Kinetics; D009961:Orosomucoid / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects*; D012709:Serum Albumin / Q000378:metabolism; D013237:Stereoisomerism; D047391:alpha-Cyclodextrins / Q000737:chemistry
chemical_list: D000418:Albumins; D001798:Blood Proteins; D009961:Orosomucoid; D012709:Serum Albumin; D047391:alpha-Cyclodextrins; D017311:Amlodipine; C032613:alpha-cyclodextrin