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 antithromboti c agent aspalatone ([3-[2-methyl-4-pyronyl)]-2-acetyloxybenzoate, CAS 147249-33-0), the metabolism and disposition of aspalatone were compar ed with those of acetylsalicylic acid (ASA) in the gut wall in relatio n to the salicylate level in the stomach tissues following oral admini stration in pyrolus-ligated rats. Both aspalatone and ASA were essenti ally stable in gastric juice and were absorbed in stomach unchanged. I n glandular portion of the stomach, salicylate level found at 10 min p ost-dose in aspalatone (80 mg/kg) - and in ASA (50 mg/k)-treated group was 67 +/- 43 mnol/g tissue and 2000 +/- 250 nmol/g tissue, respectiv ely. In non-glandular (rumen) tissue, salicylate was not detected in t he 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 st ability of the ester bond connecting the salicylic acid and maltol gro ups 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.