Development and Validation of a Pig Model for Colon-specific Drug Delivery

Abstract

The purpose of this investigation was to develop a pig model for colonic drug delivery and to validate the model by determining whether the physiology of the pig colon had been significantly altered after the surgical implantation of a gut cannula into the terminal ileum of the pig. A fistula was created in the terminal ileum of the pig, and a cannula fitted for the purpose of directly administering drug formulations to a point just anterior to the ileocaeco-colonic valve of the gastrointestinal tract. The cephalic vein of the pig was also cannulated to enable continued blood sampling. Sulphasalazine was used as the model drug for the validation study. In the intact colon, sulphasalazine is metabolized by the gut microflora to sulphapyridine which is then absorbed. Sulphasalazine was administered orally to non-fistulated and fistulated pigs and then ileally, via the gut cannula, to fistulated pigs. Absorption of sulphapyridine was monitored by HPLC analysis of plasma samples. There was no significant difference in the absorption obtained for the three groups. Thus it is demonstrated that the colon physiology had not been altered. The colonic pig model is ideal for studying factors affecting the colonic absorption of drugs and as a means for developing drug delivery systems with improved absorption properties.

Gastrointestinal transit of dosage forms in the pig

“…Animal models are valuable for the evaluation of the gastrointestinal absorption of new chemical entities and the performance of novel dosage forms. The rat is considered to be a good model for studying the absorption of drug substances (Gardner et al 1996) ; however, due to its size, it is not suitable for investigations on oral dosage forms intended for administration to man. The dog has been considered by many groups as a popular model, but unfortunately the gastrointestinal tract is not physiologically comparable with that of man (Gardner et al 1996).…”

“…The rat is considered to be a good model for studying the absorption of drug substances (Gardner et al 1996) ; however, due to its size, it is not suitable for investigations on oral dosage forms intended for administration to man. The dog has been considered by many groups as a popular model, but unfortunately the gastrointestinal tract is not physiologically comparable with that of man (Gardner et al 1996). The pig is considered to be the most suitable non-primate animal model since it resembles the human situation better than any other non-primate animal species with regard to eating behaviour, anatomy and physiology of the gastrointestinal tract (Fleming & Arce 1986 ;Kararli 1995).…”

Intestinal Toxicity Induced by 5-Fluorouracil in Pigs: A New Preclinical Model

“…Additionally, patterns of intestinal enzyme development and their regulation are similar to those found in humans [15] , and pig intestinal mucosal immunology aspects are homologous to those of humans [16,17] . Intestinal epithelial cells have been employed for studying cytotoxic properties of luminal compounds [18] and to develop drug delivery systems with improved absorption properties [19] . Moreover, pigs are more tolerant to immunosuppression than other animals, and have been used extensively in recent decades to study organ transplantation [20] .…”

Pros and cons of methods used for the prediction of oral drug absorption

“…One important feature of this species is that the morphology of the large intestine is similar to humans [106,118]. A colonic pig model has been proposed for studying factors affecting the colonic absorption of drugs and as a means for developing drug-delivery systems with improved absorption properties [127]. Some physiological features in the GI tract (i.e., the incomplete food gastric emptying, the presence of gastric ulcers) have to be considered when pigs are used in absorption studies [118].…”