PT  - JOURNAL ARTICLE
AU  - J D Huang
AU  - S Oie
TI  - Effect of altered disopyramide binding on its pharmacologic response in rabbits.
DP  - 1982 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 469--471
VI  - 223
IP  - 2
4099  - http://jpet.aspetjournals.org/content/223/2/469.short
4100  - http://jpet.aspetjournals.org/content/223/2/469.full
SO  - J Pharmacol Exp Ther1982 Nov 01; 223
AB  - This study was undertaken to determine whether pharmacologic response to disopyramide is related to unbound or to total plasma concentration. Pharmacologic response, measured as changes in QRS duration of the EKG, 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. These results demonstrate that the unbound concentrations of disopyramide in plasma are a better measure of the pharmacologic response than is the total plasma concentration.