GASTRO-INTESTINAL ABSORPTION OF PARACETAMOL IN THE RAT

The absorption of [3H]paracetamol by rat small intestine, colon and stomach was studied in vivo and in vitro. Small intestinal in vivo studies, using a wide range of drug concentrations, showed that absorption was efficient and uniform throughout the small bowel, no site showing preferential absorption. Double reciprocal and direct plots indicated 1st order kinetics. The pattern was not observed when uptake was occurring from high concentrations of paracetamol in suspension. Gastric and colonic in vivo studies showed that there was appreciable absorption of [3H]paracetamol from these sites. In vitro studies using everted intestinal sacs showed no effect on paracetamol transfer when the incubation temperature was lowered to 10.degree. C or when iodoacetate (5 .times. 10-2 M) and 2,4 dinitrophenol (5 .times. 10-4 M) were added to the incubation medium. There was a significant reduction in transfer of paracetamol against a concentration gradient of 10:1 applied across the mucosa. The uptake of paracetamol may occur by a passive transport process; the efficiency of paracetamol absorption observed indirectly by others was confirmed.