Effect of Salicylate on the Fate of Bishydroxycoumarin in the Rat

Abstract

Salicylate increased the rate of elimination of 14C-bishydroxycoumarin from the blood during the first 7 h after administration. A tissue distribution study showed most of the radioactivity to be found in liver, blood, lung, and kidney. Salicylate treatment increased the concentration of radioactivity in the liver and decreased it in blood, but had little effect in the other tissues. Biliary excretion of radioactivity was increased from 12.3 ± 2.7 to 29.3 ± 2.5% of the dose in the 0–6 h period by salicylate. Total urinary and fecal excretion was little affected. An in vitro plasma protein study showed that salicylate displaces bound bishydroxycoumarin. A similar effect was observed in vivo. It is concluded that salicylate increases the initial rate of bishydroxycoumarin elimination by displacing some of the bound drug from plasma proteins, thereby facilitating uptake into the liver where the drug is metabolized and excreted.