Aspirin Intolerance: Experimental Models for Bed-to-Bench

Yamashita, Masamichi

Aspirin is an anti-inflammatory analgesic agent that has been marketed since 1899 and is the oldest chemically syn- thesized drug (Fig. 1a) . In the 1970s, it was found that the mechanism of action of aspirin and other acidic NSAIDs involves inhibition of PG production [43] [44] [45] . In the 1990s, the molecular mechanism of aspirin was finally revealed to be irreversible acetylation of Ser-530 on COX [46] , with inhibition of both COX-1 and COX-2 [23] , while most NSAIDs such as indomethacin (Fig. 1b) reversibly inhibit COX. Almost all (80-100%) the oral dose of aspirin (100-300 mg) is immediately absorbed from the stomach or upper small intestine and the maximum serum concentration is reached within 35 min. Then it is metabolized into salicylic acid ( Fig. 3a) and conjugated with a glucuronate or sulfate. A sodium salt of the one of the metabolites, gentisic acid ( Fig. 3b) , is reported to have an anti-inflammatory effect [47] .