Tissue distribution kinetics of tetraethylammonium ion in the rat

Tissue distribution kinetics of tetraethylammonium (TEA) ion in rats were studied following both constant-rate intravenous infusion and rapid intravenous injection of the drug. At a steady-state plasma concentration of 0.2 microgram/ml, the tissue-to-plasma (T/P) concentration ratio of the kidneys, liver, heart, gut, and lungs exceeded 1, indicating that TEA is localized in these tissues. In vitro tissue homogenate binding and slice uptake experiments provided no evidence of TEA binding to tissue constitutents, suggesting that the high T/P concentration gradient is due to an active transport process. The maximum concentration of TEA in all tissues occured with 5-15 min after rapid injection of a 2-mg dose. Except for the liver, the subsequent decline of TEA concentration in various tissues over a 5-hr period was slow compared to that in plasma. Consequently, the T/P ratio of liver and kidney remained relatively constant, while those of the other tissues increased continually with time. These features of TEA tissue distribution kinetics can be predicted by a physiologically based pharmacokinetic model which incorporates both active and passive transport processes for the passage of TEA between blood and the tissue mass.