N. Gardner et al., DEVELOPMENT AND VALIDATION OF A PIG MODEL FOR COLON-SPECIFIC DRUG-DELIVERY, Journal of Pharmacy and Pharmacology, 48(7), 1996, pp. 689-693
The purpose of this investigation was to develop a pig model for colon
ic drug delivery and to validate the model by determining whether the
physiology of the pig colon had been significantly altered after the s
urgical implantation of a gut cannula into the terminal ileum of the p
ig. A fistula was created in the terminal ileum of the pig, and a cann
ula fitted for the purpose of directly administering drug formulations
to a point just anterior to the ileocaeco-colonic valve of the gastro
intestinal 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 abso
rbed. Sulphasalazine was administered orally to non-fistulated and fis
tulated pigs and then ileally, via the gut cannula, to fistulated pigs
. Absorption of sulphapyridine was monitored by HPLC analysis of plasm
a samples. There was no significant difference in the absorption obtai
ned for the three groups. Thus it is demonstrated that the colon physi
ology had not been altered. The colonic pig model is ideal for studyin
g factors affecting the colonic absorption of drugs and as a means for
developing drug delivery systems with improved absorption properties.