Effects of metoxibutropate, ibuprofen and guaiacol on the gastrointestinal system.
In previous studies we have shown that ibuprofen, guaiacol and the guaiacol ester of ibuprofen (I.N.N. metoxibutropate) are able to inhibit in-vitro prostaglandin synthesis. In the present study we have evaluated the effect of ibuprofen, guaiacol and metoxibutropate on the gastrointestinal system. Oral treatment with equimolar increasing doses of the three drugs produced a progressive inhibition of prostaglandin biosynthesis in the intestinal tract, without any effect on the rate of intestinal propulsion. Further studies evaluated the gastric tolerance of a molar dose of ibuprofen causing ulceration in 50% of the animals. After single and repeated administration of guaiacol and of the guaiacol ester of ibuprofen, the percentage of animals with gastric damage was very low and the index of ulceration seemed rather moderate. Our results show that although guaiacol is able to inhibit prostaglandin biosynthesis like a classic NSAID, it does not induce gastric damage. For these reasons it is justified to combine guaiacol with ibuprofen in order to reduce gastric erosions induced by a classic antiinflammatory drug.
Fossati
A
A
Research and Development, Formenti Pharmaceutical Co., Origgio, Italy.
Vimercati
M G
MG
Bozzi
M
M
Passarotti
C
C
Bandi
G L
GL
Formenti
A
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002368:Castor Oil / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced; D004064:Digestive System / Q000187:drug effects*; D004068:Digestive System Physiological Phenomena; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects; D006139:Guaiacol / Q000494:pharmacology* / Q000031:analogs & derivatives; D007052:Ibuprofen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; C020176:metoxibutropate; D006139:Guaiacol; D002368:Castor Oil; D007052:Ibuprofen