Effects of sodium 5-methoxysalicylate on macromolecule absorption and mucosal morphology in a vascularly perfused rat gut preparation in vivo.
The effect of sodium 5-methoxysalicylate on absorption was assessed by measurement of the appearance of test compounds in the portal blood output of a perfused rat gut model. The test compounds were a hexapeptide analogue of somatostatin, insulin, and horseradish peroxidase. Considerable amounts of sodium 5-methoxysalicylate were present in the portal blood 10 min after intraduodenal administration. When co-administered with sodium 5-methoxysalicylate (60 mg), a marked increase in the concentrations of the test substances occurred at t = 15 min which lasted for a further 15 min. Quantities of less than 60 mg had much reduced adjuvant effects. In control experiments with no adjuvant, the concentrations of the test substances remained low throughout the 1-h period of blood collection. After the administration of 60 mg of sodium 5-methoxysalicylate, slight mucosal damage was apparent at 10 min. This became progressively worse with time and, at 1 h, extensive mucosal stripping had occurred. The results suggest, although they do not prove, that apparent adjuvant effects in the small intestine may be a direct consequence of serious mucosal damage. This means that care must be taken in the investigation of adjuvant properties to exclude the possibility that an observed increase in transport is due to gross loss of integrity of the membrane.
Peters
G E
GE
Research Centre, Ciba-Geigy Pharmaceuticals, Horsham, West Sussex, UK.
Hutchinson
L E
LE
Hyde
R
R
McMartin
C
C
Metcalfe
S B
SB
D000818:Animals; D006735:Horseradish Peroxidase; D062425:Hydroxybenzoate Ethers; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains; D012459:Salicylates / Q000494:pharmacology*
D062425:Hydroxybenzoate Ethers; D007328:Insulin; D012459:Salicylates; C033304:5-methoxysalicylic acid; D006735:Horseradish Peroxidase