Assessment of gastric antisecretory effects of phenoxyisobutyrate derivatives in the rat and the mouse.
After the observation of a low incidence of gastric carcinoid tumours in rats, but not in mice, given ciprofibrate for 2 years, ciprofibrate and related compounds were investigated for gastric antisecretory activity. A significant inhibition of gastric secretion, similar to that induced by comparable doses of cimetidine, was observed in the fischer rat 1.5 h after a single oral (200 or 500 mg kg-1) or intraduodenal (100 or 300 mg kg-1) administration of ciprofibrate, bezafibrate, and clofibric acid. Ciprofibrate had prolonged antisecretory activity when compared with bezafibrate or ranitidine. Prolonged inhibition of gastric secretion is proposed as the primary cause of gastric carcinoids in the rat, since in a comparative evaluation, antisecretory activity was observed in the rat but not in the mouse.
Eason
C T
CT
Toxicology Dept., Sterling-Winthrop Research Centre, Alnwick, Northumberland, U.K.
Pattison
A
A
Howells
D D
DD
Spencer
A J
AJ
Bonner
F W
FW
D000284:Administration, Oral; D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology*; D002276:Carcinoid Tumor / Q000139:chemically induced; D002994:Clofibrate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D058607:Fibric Acids; D005750:Gastric Juice / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013274:Stomach Neoplasms / Q000139:chemically induced; D013997:Time Factors
D058607:Fibric Acids; D002995:Clofibric Acid; C019304:ciprofibrate; D002994:Clofibrate; D001629:Bezafibrate