Studies on disposition and metabolism of tolmetin, a new anti-inflammatory agent, in rats and mice. I. Absorption, distribution, and excrection of [14C]tolmetin radioactivity.

[14C]Tolmetin was rapidly and almost completely absorbed in both rats and mice. The major portion of the drug was shown to be absorbed from the upper part of the duodenum, and a small portion from the stomach. Tissue levels of radioactivity comparable to blood levels were found only in liver and kidney, and other tissue levels were lower than those in blood, possibly because of the considerable plasma protein binding of the drug. Radioactivity disappeared from most tissues at rates similar to that from blood, and no appreciable radioactivity was found in rat and mouse tissues 24 hr after dosing. Correspondingly, radioactivity was excreted mostly in urine within this time period. Mouse fetuses contained significantly less radioactivity than did maternal tissues in autoradiography. No significant differences were found in absorption, distribution, and excretion of radioactivity when single or five consecutive daily doses of [14C]tolmetin were administered to rats.