Aspirin-induced gastric mucosal damage: prevention by enteric-coating and relation to prostaglandin synthesis.
1. Gastric damage induced by low-dose aspirin and the protective effect of enteric-coating was assessed in healthy volunteers in a double-blind placebo-controlled cross-over trial using Latin square design. Each was administered placebo, plain aspirin 300 mg daily, plain aspirin 600 mg four times daily, enteric-coated aspirin 300 mg daily, or enteric-coated aspirin 600 mg four times daily for 5 days. Gastric damage was assessed endoscopically, and gastric mucosal bleeding measured. 2. Aspirin 300 mg daily and 600 mg four times daily caused significant increases in gastric injury compared with placebo. Gastric mucosal bleeding was significantly more with the high dose, with a trend towards increased gastric erosions, compared with the low dose. 3. Enteric-coating of aspirin eliminated the injury caused by low dose aspirin and substantially reduced that caused by the higher dose. 4. All dosages and formulations caused similar inhibition of gastric mucosal prostaglandin E2 synthesis. 5. Serum thromboxane levels were suppressed equally with plain and enteric-coated aspirin. 6. In this short-term study in healthy volunteers, gastric toxicity from aspirin was largely topical, independent of inhibition of prostaglandin synthesis, and could be virtually eliminated by the use of an enteric-coated preparation.
Hawthorne
A B
AB
Department of Therapeutics, University Hospital, Nottingham.
Mahida
Y R
YR
Cole
A T
AT
Hawkey
C J
CJ
D000328:Adult; D001241:Aspirin / Q000009:adverse effects*; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000517:prevention & control; D006801:Humans; D008297:Male; D012459:Salicylates / Q000097:blood; D013272:Stomach Diseases / Q000139:chemically induced* / Q000517:prevention & control; D013608:Tablets, Enteric-Coated; D013929:Thromboxane B2 / Q000097:blood
D012459:Salicylates; D013608:Tablets, Enteric-Coated; D013929:Thromboxane B2; D015232:Dinoprostone; D001241:Aspirin