Quinidine and dihydroquinidine interactions in human plasma

Abstract

The protein-binding characteristics of dihydroquinidine, a known impurity in drug grade quinidine, in human plasma and the effects of dihydroquinidine on quinidine interactions with these plasma constituents were studied by equilibrium dialysis. In the plasma concentration range of 1.75-23.0 mg/liter, dihydroquinidine binding was similar to the binding observed with quinidine. The data suggested the presence of a single class of binding sites for both compounds in the plasma drug concentration range and samples studied. The mean values for the association constant, K, and the total concentration of binding sites, nPt, for dihydroquinidine were 4.75 +/- 0.67 X 10(4) M-1 and 5.78 +/- 0.17 x 10(-5) M, respectively. The corresponding values for quinidine were 4.78 +/- 1.00 x 10(4) M-1 and 5.65 +/- 0.48 x 10(-5) M. In the presence of 5 and 10% (of total alkaloid content) dihydroquinidine, the plasma concentration of unbound quinidine did not change significantly. At a 20% level of dihydroquinidine, however, an increase in unbound quinidine was observed (p less than 0.05). The elevations in free quinidine concentrations were directly related to the level of dihydroquinidine present. The results of this study indicate that the interactions between dihydroquinidine and quinidine for binding sites on human plasma proteins are competitive.