IMPAIRMENT OF SALICYLATE UPTAKE FROM RAT SMALL-INTESTINE FOLLOWING PRETREATMENT WITH A FOLIC-ACID ANTAGONIST

The effect of amethopterin, a folic acid antagonist, on salicylate which is not absorbed from the rat small intestine by an active process and its uptake in vivo were examined. Pretreatment of rats with amethopterin prior to pertusion of the gut with sodium salicylate significantly (P = < 0.001 - < 0.05) lowered blood salicylate. This reduction appears to bear a direct relation to reduced mucosal depth found at different concentrations of amethopterin. Amethopterin was reported by Vitale, Zamcheck and others (1954) to damage mucosal cells and to promote the formation of cubical or pavement cells instead of the normal columnar form. In this study such cells were observed at doses of 20 and 40 mg kg-1, but distribution was irregular, and it was not possible to assess the proportion of atypical cells. Some changes in mucin distribution were seen in sections from treated animals but could not be evaluated quantitatively. Whether the changes in cell structure or mucin distribution affected the passage of salicylate from lumen to blood is unclear, but since experimental conditions which might have affected uptake (pH and perfusion rate) were kept constant, probably the reduced area was a major factor in the decreased concentration of blood salicylate, and the use of folic acid inhibitors may result in diminished uptake of other drugs.