title: Stereoselective binding of propranolol to human plasma, alpha 1-acid glycoprotein, and albumin.
abstract: Our aim was to determine possible stereoselectivity in the plasma binding of propranolol. Equilibrium dialysis with plasma from seven healthy subjects and a deuterium-labeled pseudoracemate of propranolol was used. Plasma binding of the propranolol enantiomers differed with the unbound fraction of (-)-propranolol (22 +/- 2%; mean +/- SE) being smaller than that of (+)-propranolol (25.3 +/- 1.9%). The (-)/(+)-propranolol ratio for the unbound fraction, a measure of the stereoselectivity, was 0.86 +/- 0.02. There was an inverse correlation between the unbound (-)/(+)-propranolol ratio in individual subjects and overall binding of (+/-)-propranolol, indicating greater stereoselectivity at higher total binding. To assess the site of the stereoselective binding to plasma proteins, the binding of (+)- and (-)-propranolol to human alpha 1-acid glycoprotein (AGP) and human serum albumin (HSA) was examined. The binding to AGP was stereoselective for (-)-propranolol with a (-)/(+)-propranolol ratio for the unbound fraction of 0.79 +/- 0.01, whereas (+)-propranolol was bound to a greater extent to HSA with a (-)/(+)-propranolol ratio for the unbound fraction of 1.07 +/- 0.01. Although these results demonstrate opposite stereoselectivity in the binding of (+)- and (-)-propranolol to AGP and HSA, the stereoselective binding of (-)-propranolol to AGP predominates in plasma. This stereoselective plasma binding of the (-)-enantiomer of propranolol could limit the access of this more active enantiomer to beta-receptors or other active sites. The uptake of propranolol by red blood cells was not stereoselective.
mesh_terms: D000328:Adult; D003903:Deuterium; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D009961:Orosomucoid / Q000378:metabolism*; D011433:Propranolol / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D009961:Orosomucoid; D012709:Serum Albumin; D011433:Propranolol; D003903:Deuterium