Assessment of the contribution of α1-acid glycoprotein to the serum binding of basic drugs using serum treated with sulphosalicylic acid and DEAE-cellulose

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Abstract
Treatment of human serum with DEAE-cellulose in acid conditions almost completely removed α1-acid glycoprotein (α1-AG) with little change in the concentration of albumin and β-lipoprotein, while treatment with sulphosalicylic acid removed almost all the proteins except α1-AG. The binding of various drugs to serum treated as above was measured by equilibrium dialysis and the contribution of α1-AG to drug binding by human serum was assessed. Sulphosalicylic acid-treated serum exhibited a saturable binding for propranolol, which was considered to be due to the binding to α1-AG while DEAE-cellulose-treated serum mostly exhibited non-saturable binding, for which albumin and β-lipoprotein may be responsible. With this treated serum, α1-AG was estimated to contribute approximately 40% to the binding of therapeutic concentrations of propranolol, 15% to that of imipramine and 15-20% to that of desipramine, respectively, in serum samples pooled from healthy adults. However, no contribution of α1-AG was observed in the binding of salicylic acid to the serum. Dissociation constants of the propranolol binding to the high affinity site in control serum, sulphosalicylic acid-treated serum and purified α1-AG showed similar values (3.7-6.7 μM). These results suggest that treatment of serum with sulphosalicylic acid and DEAE cellulose is useful in assessing the contribution of α1-AG to the serum binding of basic drugs.