Linear relationships between plasma binding and lipophilicity of disopyramide derivatives.

The extent of plasma binding and the partition coefficient of disopyramide and 20 disopyramide derivatives were determined. Structural variations on the four functional groups around the tetrahedral carbon in the disopyramide molecule was found to influence both parameters to varying degrees. Three linear equations were developed to correlate the observed effects, depending on the type of chemical modification. The linear correlation between drug-plasma interaction and lipophilic character was analyzed theoretically. A simple model was derived to relate quantitatively the variation in the extent of plasma binding to the change in lipophilicity of disopyramide derivatives.