INFLUENCE OF SHORT CHAIN FATTY ACIDS ON THE ABSORPTIVE CLEARANCE OF RANITIDINE HCl FROM RABBIT INTESTINE

Ranitidine HCl is a histamine H2-receptor antagonist reducing gastric acid secretion under daytime and nocturnal basal conditions. Ranitidine HCl is 50% absorbed after oral administration. This research was undertaken in order to examine the effect of short-chain fatty acids (SCFAs), acetate, propionate, and butyrate on the absorptive clearance of ranitidine HCl as a function of intestinal site (jejunoileum vs ascending-colon). A "through-and-through" in situ intestinal perfusion technique was adopted using the rabbit as an animal model. Coperfusion of either sodium acetate, sodium propionate, or sodium butyrate, 25 mM each, along with ranitidine HCl, 0.2 mM, allowed for an examination of increased solvent drag on intestinal permeability of this compound in both anatomical sites. The results show that ranitidine HCl is absorbed from rabbit jejunoileum as well as the ascending-colon, however the value of the absorptive clearance of this compound normalized to the intestinal length PeA/L in the ascending-colon was almost double that in the jejunoileum. A strong correlation was found between the absorptive clearance and the net water flux in both segments suggesting that the mechanism of ranitidine HCl absorption apparently consists of passive diffusion via the paracellular pathway. The negative value of anatomical reserve length ARL in both segments reflects the incomplete absorption of this compound. SCFAs had a significant effect on increasing the absorptive clearance of ranitidine HCl in both segments studied. This effect was in the order butyrate > propionate > acetate. However there was no statistical difference between the effect of butyrate and propionate. The permeability enhancing effect of SCFAs was much higher in the ascending-colon, this could be attributed to the higher Na+, Cl  , and water influx in this segment. In conclusion, marked segmental differences in the absorption of ranitidine HCl are apparent in the rabbit small and large intestine which could be significantly enhanced by the use of SCFAs