A possible contribution of phospholipids in tissue distribution of quinidine in rats.

Abstract

The tissue distribution of quinidine was investigated at three different steady-state plasma concentrations of quinidine in rats. The tissue distribution of quinidine (tissue-to-plasma concentration ratio, Ct/Cp) was studied in the liver, lung, kidney and heart and the highest distribution was found in the lung. Tissue binding characteristics of quinidine was determined in normal tissue homogenates and lipid-depleted tissue homogenates in vitro. No correlation was observed between the tissue bindings (product of association constant (K1) and number of binding sites (n), nK1) estimated in each normal tissue homogenate and the values of Ct/Cp in vivo. However, a marked decrease in the tissue binding of quinidine was observed in all lipid-depleted tissue homogenates, and the largest decrease was observed in the lung tissue. This result suggested that lipid may have an important role in the tissue binding of quinidine. However, no good relationship was observed between the values of Ct/Cp and the phospholipid contents in each tissue. In order to investigate the role of lipid in the tissue binding of quinidine, phospholipids extracted from each tissue were used for binding study. The phospholipids binding of quinidine (nK2) increased in the following order; heart less than liver less than kidney less than lung, and the plots of the values of Ct/Cp obtained in vivo against the binding ability of phospholipids (product of nK2 and the content of phospholipid in each tissue) gave a good linear relationship. Based on these observations, it was concluded that some species of phospholipids had an important and determining role in the tissue distribution of quinidine in vivo.