Net secretion of furosemide is subject to indomethacin inhibition, as observed in Caco-2 monolayers and excised rat jejunum

Purpose. To determine if intestinal secretion occurs for the poorly bioavai lable diuretic, furosemide. Methods. Jejunal segments of male Sprague-Dawley rats were mounted on diffu sion chambers, and the permeation of furosemide was measured across the exc ised tissue in both directions. Studies were repeated using cultured epithe lia from adenocarcinoma cells (Caco-2) grown on filter inserts mounted in 6 -well plates. Temperature-dependence and chemical inhibition by indomethaci n was also tested using the cell culture model. Results. Net secretion from rat intestine of over 3-fold was observed for 2 0 mu M furosemide. Net secretion of furosemide by Caco-2 cells was over 300 % greater than for intestinal segments (10-fold vs. 3-fold). For both model s, a decrease in furosemide transport in the direction of secretion was obs erved in the presence of indomethacin (100 mu M). although only results usi ng the Caco-2 cells showed an increase in the absorptive transport. Furosem ide secretion from Caco-2 cells decreased with decrease in temperature from 37 degrees C to 4 degrees C, suggesting a carrier-mediated process. Conclusions. Furosemide appears to be secreted in the small intestine. Thes e: preliminary results indicate that furosemide bioavailability may be limi ted by an intestinal transporter.