EFFECT OF ALTERED DISOPYRAMIDE BINDING ON ITS PHARMACOLOGIC RESPONSE IN RABBITS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 223  (2) , 469-471
Abstract
Whether the pharmacologic response to disopyramide [an antiarrhythmic agent] is related to unbound or to total plasma concentration was studied. Pharmacologic response, measured as changes in QRS duration of the ECG, was determined in rabbits at various steady-state concentrations of disopyramide under normal and altered plasma protein binding conditions. Plasma protein binding was increased by injection of 40 mg/kg of human glycoprotein fraction VI. The concentration-response curve for total concentration was displaced toward higher concentrations after increasing the plasma protein binding of disopyramide. The concentration-response curves obtained for unbound drug with and without the increased binding were superimposable. The displacement of the concentration-response curve for total drug was identical to the increase in concentration of the bound drug in plasma. The unbound concentrations of disopyramide in plasma are a better measure of the pharmacologic response than is the total plasma concentration.