SITE-DEPENDENT SMALL-INTESTINAL ABSORPTION OF RANITIDINE

The site-dependent, small intestinal absorption characteristics of ran itidine were estimated by the intestinal steady state perfusion techni que (triple lumen tubing system) combined with simultaneous measuremen t of serum concentrations of ranitidine. Ranitidine 150 mg . l(-1) was perfused at 10 ml . min(-1) for 180 min in different sites of the sma ll intestine between 65-250 cm beyond the teeth. Each of 9 healthy, ma le volunteers was examined twice. using perfusion sites in different r egions of the small intestine to permit intraindividual comparisons. T he absorption rates (mu g . 30 cm(-1) . min(-1)) calculated from intes tinal samples showed distinct site-dependence; the highest rates (medi ans 160-923 mu g . 30 cm(-1) . min(-1)) were found in the most proxima l region (duodenojejunal junction), and the most distal perfusion site s (distal jejunum/ileum) showed median rates from 193 to 265 mu g . 30 cm(-1) . min(-1). In both of these regions there was a significant po sitive correlation between the net intestinal water flux and the movem ent of ranitidine. Within the mid-jejunum, every subject showed marked secretion of ranitidine into the gut lumen (medians - 338 to - 124 mu g . 30 cm(-1) . min(-1)), and in this region there was no influence o f water flux on ranitidine movement. The intraluminal results were con firmed by the corresponding site-dependent areas under the serum conce ntration-time curves (AUC), which decreased with the distance of the p erfusion site from the teeth. After the more distal perfusions individ ual AUCs amounted to 64-16% of the AUCs obtained after more proximal a pplications. The results demonstrate the small intestine as the site o f a gradient of absorption of ranitidine. Changes in net water movemen t along the small intestine can be assumed to influence the absorption pattern of ranitidine.