PARACETAMOL ABSORPTION FROM DIFFERENT SITES IN THE HUMAN SMALL-INTESTINE

Site-specificity in the small intestinal absorption of paracetamol was investigated using a segmental intestinal steady state perfusion technique (triple-lumen tubing system) combined with simultaneous measurements of serum drug concentrations. Dissolved paracetamol was perfused over 160 min into different parts of the small intestine (65-210 cm beyond the teeth). Each of the four healthy subjects was studied twice with a proximal and a more distal site of perfusion. Serum drug concentrations were similar after proximal and distal perfusions. Mean drug absorption rates calculated from intestinal aspirate concentrations were similar in both parts of the intestine-proximal: 869 mu g 30 cm(-1) min(-1) (95% CI: 659-1079) vs distal: 941 mu g 30 cm(-1) min(-1) (794-1088). The absorption rate was related directly to the amount of paracetamol perfused per unit time as well as to the rate of transmucosal water fluxes.