Development and validation of a pig model for colon-specific drug delivery.
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.
Gardner
N
N
Danbiosyst UK Ltd, Albert Einstein Centre, Nottingham, UK.
Haresign
W
W
Spiller
R
R
Farraj
N
N
Wiseman
J
J
Norbury
H
H
Illum
L
L
D000818:Animals; D019540:Area Under Curve; D003106:Colon / Q000378:metabolism*; D005765:Gastrointestinal Agents / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D012460:Sulfasalazine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013552:Swine
D005765:Gastrointestinal Agents; D012460:Sulfasalazine