Plasma protein binding of basic drugs

Abstract

The protein binding of a number of basic drugs has been shown to be inhibited when blood is collected in Vacutainer tubes. We found that the plasticizer tris(2‐butoxyethyl) phosphate (TBEP). present in plasma collected in Vacutainers. was a potent inhibitor of alprenolol and imipramine protein binding. Its concentration in the plasma could quantitatively explain the displacement phenomenon. Alprenolol binding to a solution of a physiologic concentration (0.67 gmlL. 0.015 mM) of α1‐acid glycoprotein (orosomucoid) was decreased from 76% to 16% by addition of 10 uglml (0.026 mM) of TBEP. while imipramine binding was decreased from 69% to 13%. Alprenolol and imipramine binding to albumin and lipoproteins was virtually unchanged by TBEP. Due to its selective effect on binding to α1‐acid glycoprotein. TBEP may be a useful tool for studying plasma protein binding of basic drugs.