Pharmacological studies in the rat with [2-(1,3-didecanoyloxy)-propyl]2-acetyloxybenzoate (A-45474): an aspirin pro-drug with negligible gastric irritation.
A triglyceride of aspirin, A-45474: [2-(1,3-didecanoyloxy)-propyl]2-acetyloxybenzoate, was developed to reduce the direct gastric irritant properties of aspirin. Studies in the rat show that oral administration of A-45474 produces anti-inflammatory activity comparable to aspirin with negligible gastric irritation. Compared with aspirin, plasma salicylate levels of A-45474 appeared less rapidly and were more sustained. It is concluded that incorporation of aspirin in the 2-position of a triglyceride bearing n-decanoyl groups in the 1- and 3-positions markedly reduces the gastric irritating properties of aspirin while maintaining its pharmacological effects.
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D001682:Biological Availability; D002351:Carrageenan / Q000037:antagonists & inhibitors; D003692:Delayed-Action Preparations; D004487:Edema / Q000188:drug therapy; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D051381:Rats; D012459:Salicylates / Q000097:blood; D013270:Stomach / Q000187:drug effects*; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D012459:Salicylates; D014280:Triglycerides; C026258:(2-(1,3-didecanoyloxy)-propyl)2-acetyloxybenzoate; D002351:Carrageenan; D001241:Aspirin