The contribution of ? 1-acid glycoprotein, lipoproteins, and albumin to the plasma binding of perazine, amitriptyline, and nortriptyline in healthy man

Abstract

Parameters for the binding of perazine (PER), amitriptyline (AT) and nortriptyline (NT) to plasma and to single plasma proteins were determined by equilibrium dialysis. The highest affinity (K at least 10⁵ M⁻¹) and lowest capacity (first site 1 mol/mol) towards all three drugs was exhibited by α₁-acid glycoprotein (α₁-AGP). From the parameters, α₁-AGP was estimated to contribute 43% to total binding of PER and 49 and 31%, respectively, to AT and NT binding in samples with normal protein concentrations. Fractions bound to total lipoproteins would amount to 32% (PER), 40% (AT) and 52% (NT), respectively, while the contribution of albumin would range from 11% (AT) to 25% (PER). The extent of the binding to plasma was compared with that to single proteins and their mixtures. Binding to combinations of α₁-AGP, lipoproteins and albumin exceeded that to plasma with PER, but not with AT and NT. This leads to the assumption that additional plasma constitutents interfere with PER binding.