Different binding of propranolol enantiomers to human alpha1-acid glycoprotein

Abstract The binding of propranolol enantiomers to human alpha 1 -acid glycoprotein was studied using high performance liquid chromatography in order to provide insight into binding models and to describe individual binding parameters of both enantiomers. The binding of (−)-propranolol was shown to be saturable with one major binding site ( n = 0.81, k = 2.73 × 10 5 / M ). The saturation process achieved its upper asymptotic value at drug/protein molar ratio of approximately 1. In the case of the opposite (+)- enantiomer the binding isotherm did not show evidence of saturation even at higher drug/protein molar ratios (up to 50). The individual binding parameters for (+)-enantiomer were n = 0.38, k = 3.4 × 10 6 /M and n ′ k ′ = 1.39 × 10 4 /M for the saturable and nonsaturable binding component, respectively. At drug/protein molar ratio 2 the circular dichroism measurements confirmed the existence of different binding models for individual propranolol enantiomers.