MECHANISM OF INTESTINAL-ABSORPTION OF RANITIDINE AND ONDANSETRON - TRANSPORT ACROSS CACO-2 CELL MONOLAYERS

We have investigated the transport of ranitidine and ondansetron acros s the Caco-2 cell monolayers. The apparent permeability coefficients ( P(app)) were unchanged throughout the concentration range studied, ind icating a passive diffusion pathway across intestinal mucosa. No metab olism was observed for ranitidine and ondansetron during the incubatio n with Caco-2 cell monolayers. P(app) values for ranitidine and ondans etron (bioavailability of 50 and approximately 100% in humans, respect ively) were 1.03 +/- 0.17 x 10(-7) and 1.83 +/- 0.055 x 10(-5) cm/sec, respectively. The P(app) value for ranitidine was increased by 15- to 20-fold in a calcium-free medium or in the transport medium containin g EDTA, whereas no significant change occurred with ondansetron, indic ating that paracellular passive diffusion is not rate determining for ondansetron. Uptake of ondansetron by Caco-2 cell monolayers was 20- a nd 5-fold higher than that of ranitidine when the uptake study was car ried out under sink conditions and at steady state. These results sugg est that ranitidine and ondansetron are transported across Caco-2 cell monolayers predominantly via paracellular and transcellular pathways, respectively.