Stereoselective binding of propranolol to human plasma, α 1 ‐acid glycoprotein, and albumin

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 α 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 β‐receptors or other active sites. The uptake of propranolol by red blood cells was not stereoselective. Clinical Pharmacology and Therapeutics (1983) 34 , 718–723; doi: 10.1038/clpt.1983.240