Salicylate levels in rat stomach tissues after administration of aspalatone and acetylsalicylic acid in relation to their ulcerogenicity.

To study the mechanism for the low ulcerogenicity of the antithrombotic agent aspalatone ([3-[2-methyl-4-pyronyl)]-2-acetyloxybenzoate, CAS 147249-33-0), the metabolism and disposition of aspalatone were compared with those of acetylsalicylic acid (ASA) in the gut wall in relation to the salicylate level in the stomach tissues following oral administration in pyrolus-ligated rats. Both aspalatone and ASA were essentially stable in gastric juice and were absorbed in stomach unchanged. In glandular portion of the stomach, salicylate level found at 10 min post-dose in aspalatone (80 mg/kg)-and in ASA (50 mg/kg)-treated group was 67 +/- 43 nmol/g tissue and 2000 +/- 250 nmol/g tissue, respectively. In non-glandular (rumen) tissue, salicylate was not detected in the aspalatone group, whereas it reached a concentration of up to 1100 +/- 130 nmol/g tissue in the ASA group. As a result of the relative stability of the ester bond connecting the salicylic acid and maltol groups towards hydrolysis in the stomach and entrapment of ASA due to ion trapping, a lower salicylate level was observed in the stomach after oral aspalatone administration, and this may, at least in part, be the underlying mechanism for the low ulcerogenicity of aspalatone.