Binding of oxprenolol and propranolol to serum,albumin and α1-acid glycoprotein in man and other species

Species differences in binding of basic drugs have only occasionally been studied and we have therefore measured the binding of the β-adrenergic blockers oxprenolol and propranolol in (1) serum of healthy humans, dogs, rats and rabbits and of rabbits with experimental arthritis, (2) a solution of albumin of these species and (3) a solution of human α₁-AGP. In humans, dogs, rats and arthritic rabbits, binding of oxprenolol and propranolol was much higher in serum than in albumin solution; in healthy rabbits serum binding was very low and not different from albumin binding. For both drugs, concentration-dependency was seen in serum of dogs, humans and rats and of arthritic rabbits; a similar concentration-dependency was found for human α₁-AGP solution, but not for human albumin and for serum of healthy rabbits.Tris (2-butoxyethyl)-phosphate (TBEP), a known displacer of drugs from α₁-AGP in humans, decreased binding in serum of all species except the rabbit. For both β-blockers, species differences in capacity constants were found; species differences in affinity constants were present only for propranolol. These results suggest that in humans, dog and rat, but much less in rabbits, oxprenolol and propranolol bind mainly to α₁-AGP and that binding to α₁-AGP is more important for oxprenolol than for propranolol.