Characteristic difference in gastrointestinal excretion of clarithromycin and roxithromycin

Excretion characteristics of two new macrolides; clarithromycin and roxithromycin, into the intestinal and the gastric lumens was studied by in situ single‐pass perfusion and loop methods in rats. Roxithromycin maintained higher serum levels than clarithromycin after their intravenous administrations at a dose of 5 mg kg−1 each. Radioactivities of clarithromycin and roxithromycin exsorbed into the intestinal lumen were 8.6 and 18.9% of dose in 2 h, respectively, whereas clarithromycin and roxithromycin excreted into the bile were 28.4 and 5.9%, respectively. These results suggest that roxithromycin is transported mainly by exsorption across the intestinal membrane, whereas clarithromycin mainly by excretion through the biliary tract. On the other hand, radioactivities of clarithromycin and roxithromycin exsorbed into the gastric lumen were much less then those into the intestinal lumen and were 0.72 and 1.34% of dose in 4 h, respectively. Thus, the exsorption into the gastric lumen seems to be a minor route for the elimination of both macrolides. Consequently, the transport into the intestinal lumen via the intestinal membrane and/or the bile tract may play a significant role in the overall elimination of both macrolides. © 1998 John Wiley & Sons, Ltd.