Physiological disposition and subcellular localization of 14C-fenclorac in the rat

The physiologic disposition and subcellular tissue localization of 14C-fenclorac was studied in rats receiving single and multiple oral doses of the drug. The drug was primarily excreted via renal and fecal routes. The 24-hour urinary and fecal elimination rates were 41 and 17% respectively, of the administered dose. The daily elimination rates of drug/drug metabolites were not altered when the treatment period was extended to seven days, suggesting that the processes for the renal and fecal clearance of drug were not affected by this treatment schedule. Studies on the distribution of 14C-fenclorac in slected tissues revealed that hepatic, renal and splenic tissue to plasma ratio of the label twenty-four hours after a single dose was 1.53, 3.88 and 0.11, respectively. Similar results were observed in rats receiving multiple doses of 14C-fenclorac. The 14C-label was distributed throughout the subcellular organelles with the highest concentration in the cytosol and lower levels in the mitochondria and microsomes. Furthermore, these experiments demonstrated that both metabolic (hepatic) and excretory (kidney) organs do not accumulate fenclorac in animals receiving the drug up to seven days.