Saturation kinetics of iopanoate in the dog

Experiments were carried out in dogs with a modified Thomas cannula in the duodenum through which the common bile duct could be catheterized. Constant intravenous infusion of sodium iopanoate at different infusion rates greater than the apparent excretion maximum revealed linearity of the blood concentration with time above a threshold concentration. When the slopes of the blood curves were plotted against the known infusion rates, a straight line relationship was obtained. The X axis intercept of this straight line represents an apparent transport maximum. This value obtained from the X axis intercept matched closely with the observed excretion maximum determined from bile and urine collection. The slope of this same line equals the inverse of the volume of distribution of the drug. Although previous workers have failed to appreciate an apparent transport maximum for iopanoate, the current studies clearly demonstrate that iopanoate is excreted by a saturable mechanism. Using this technique the apparent transport maximum for iopanoate was evaluated at high and low rates of taurocholate replacement to evaluate the quantitative effect of bile salt on the apparent transport maximum. A five-fold increase in taurocholate replacement led to an average 40% increase in the apparent transport maximum of iopanoate without effecting its volume of distribution significantly.