Molecular Pharmacology, Vol 17, 187-191, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

The Distribution of Bound Propranolol between the Different Human Serum Proteins

¹ Département de Pharmacologie et Institut de Recherches sur les maladies vasculaires, Faculté de Médecine de Paris XII, 8, rue du général Sarrail F-94010 Creteil Cedex
² Département d’Informatique Médicale (Pr. Ag. Dusserre), Hôpital du Bocage F-21034 Dijon Cedex
³ Centre de Recherches ROUSSEL-UCLAF

Propranolol binding to the main, isolated, serum proteins was measured by equilibrium dialysis and compared to its overall binding in serum measured by the same method. The results showed that both saturable and nonsaturable binding phenomena exist in serum. The saturable component involves the binding of propranolol to ₁-AGP; for this interaction n = 1 and K = 30 450 M^-1. The other component represents multiple nonsaturable binding to HSA, VLDL, LDL and HDL. The nK values for HSA-propranolol binding decreased when the HSA concentration used was increased. Warfarin did not modify HSA-propranolol binding but palmitic acid decreased it at high concentrations. Propranolol and erythromycin were found to probably share the same or a close binding site on ₁-AGP. When the measured binding of propranolol to serum was simulated using the parameters obtained from the isolated protein components, the best fit was obtained by using an HSA concentration of 29 µM for the nK value. This discrepancy may be due to the extrapolation of binding parameters obtained at low HSA concentrations to the much higher protein concentrations encountered in serum.

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ACKNOWLEDGMENT We thank Dr. C. Chignell for his help in the English translation of this manuscript.