Presystemic metabolism and transport by the intestine have a major impact on bioavailability of drugs. So far it has not been possible to assess the extent of absorption and gut wall metabolism in humans. We report that drugs labeled with stable isotopes in combination with an intestinal perfusion catheter are a powerful method to study these aspects. Methods: In six subjects D7 verapamil was administered i.v. to determine hepatic clearance and simultaneously 80 mg of DO verapamil were perfused within 15 minutes at a rate of 2 ml/min in a 20 cm closed jejunal segment. The perfusate was collected in 30 ml fractions and its content determined for verapamil. At the same time plasma samples were collected and the concentrations of D0/D7-verapamil determined by LCMS. Results: The fraction of the dose absorbed ranged from 51-95% and absolute bioavailability from 15-23%. These data and the hepatic extraction ratio were used to calculate the extraction ratio by the gut wall which ranged from 31-57%. Conclusions: The data demonstrate that the use of this new developed catheter in combination with stable labelled isotopes is a powerful tool to assess absorption, metabolism and transport of drugs by the gastrointestinal tract.