The Capacity of Aspirin to Acetylate Proteins in Vitro and in Vivo

Abstract

The absorption and metabolism of aspirin has been well documented in two relatively recent reviews (Dixon et al., 1963; Smith & Smith, 1966). In the acid environment of the stomach, aspirin is in the un-ionized form and is absorbed through the gastric mucosa as such. But when it gets into the environment of the blood or duodenum, with or without the help of serum esterases, it rapidly hydrolyses into salicylic and acetic acids. This reaction is so complete and prompt that in patients taking therapeutic doses of aspirin for rheumatoid arthritis and having serum salicylate levels of 20–25 mg/100 ml (1.5–1.8 mM), only two 2 mg/100 ml (0.11 mm) is aspirin per se and the rest is in the form of sodium salicylate. Most of the salicylate ion is excreted in the urine as such, and relatively small amounts are converted to products such as glucuronides, salicyluric acid and gentisic acid. A final observation important to this discussion is the fact that 50–80% of the plasma level of aspirin and especially of salicylate ion is loosely bound to albumin, the exact amount bound being directly related to the total plasma level.