Ls. Gan et al., MECHANISM OF INTESTINAL-ABSORPTION OF RANITIDINE AND ONDANSETRON - TRANSPORT ACROSS CACO-2 CELL MONOLAYERS, Pharmaceutical research, 10(12), 1993, pp. 1722-1725
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.