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

Abstract

٥٠ % . . ٢٥ ‫ﻤﻠﻠﻰ‬ ‫ﻤﻊ‬ ٠,٢ ‫ﻤﻠﻠﻰ‬ . ‫ﺴﻴﺎﺒﻴـﺔ‬ . ‫ﻓﻰ‬ ‫ﻜﺎﻤﻼ‬ ‫ﺼﺎﺼﻪ‬ . : .. . Ranitidine HCl is a histamine H 2 -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 Mohammed A. Osman 204 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.

Influence of piperine and omeprazole on the regional absorption of Daclatasvir from rabbit intestine

“…Surgery and segment preparation were performed based on the previously reported methodology (Ashmawy et al, 2019;Osman, 2004;Osman et al, 2006;Riad & Sawchuk, 1991;Sultan et al, 2016). In brief, rabbits were fasted overnight with free admission to water before the experiment.…”

Influence of Cosolvents on the Absorptive Clearance of Ketotifen Fumarate From Rabbit Intestine, in-Situ

“…The procedures for preparation of the isolated intestinal segments for the in-situ perfusion experiment were described in details previously [11][12][13] . On the day of the study the rabbit was anesthetized using chloropromazine HCl injection (2 mg/kg) as muscle relaxant with ketamine HCl being used as the main anesthetic agent.…”

In situ evaluation of the impact of metformin or verapamil coadministration with vildagliptin on its regional absorption from the rabbit’s intestine

“…Among various techniques, an in situ intestinal perfusion technique is regarded to be the closest to in vivo parameters for permeability/transport study due to aspects such as innervation and blood supply intact. The rabbit was used as an animal model to explore the absorption of numerous drugs (Ashmawy et al., 2019; Dezani et al., 2017; Osman, 2004; Osman et al., 2006). The rabbit was chosen because of its intestinal physiological similarity to humans (Loehry et al., 1973).…”