The metabolism of aspirin in rats; localization, absorption, distribution and excretion.

By the use of acetylsalicylic acid (aspirin) 14C-labelled in either the acetyl or the carboxyl group, the metabolic pathway and the degree of degradation of the substance were studied. The change in aspirin concentration and the rate of degradation occurring in major tissues and organs after oral administration was measured by radioactivity techniques. The degree of degradation for the period 10-30 minutes was found to be about 38% in the stomach wall, 64% in the liver and 86% in the lung, and less than 10% in the circulating portion of aspirin itself in blood, under conditions of equilibrium concentration of substrate. A technique measuring 14CO2 in expired air and using 14C-acetyl aspirin allowed for determination of the kinetics of the transformation of this compound into salicylic acid. The effective period for aspirin for unstrained and unanesthetized rats given orally was determined to be 90 min. The metabolic fates of the two kinds of 14C-labelled aspirin given orally were found to be very different and characteristic by counting and autoradiographic techniques. The distribution of [carboxyl-14C] aspirin was rather uniform, but [acetyl-14C] aspirin preferentially accumulated in the bone cortex portion.