Regional differences in quinine absorption from the undisturbed human colon assessed using a timed release delivery system

Purpose. To investigate the regional absorption characteristics of the dist al gut using two markers of permeability, quinine (a transcellular probe) a nd (51)CrEDTA (a paracellular probe). Methods. The permeability markers were delivered to the undisturbed gastroi ntestinal tract in 39 healthy volunteers using an oral timed-release delive ry vehicle which allowed pulsed release within a particular site of the gut . Site of release was identified using gamma scintigraphy. Absorption of qu inine and (51)CrEDTA was assessed by measuring the percent excretion in the urine using HPLC and gamma counting respectively. Serial plasma samples al lowed time-concentration curves for quinine to be plotted. Results. There was a significant trend for diminished absorption with more distal delivery of the transcellular probe, quinine, which was: 6.26 +/- 0. 87% (small intestine, n = 10); 4.65 +/- 0.93% (ascending colon, n = 16); an d 2.59 +/- 0.52% (transverse colon, n = 10) of the ingested dose excreted r espectively (p < 0.001). No such gradient was seen with the paracellular ma rker, (51)CrEDTA. Conclusions, These results suggest that delayed release formuations shoud a im for release in the distal small bowel and proximal colon if absorption i s to be miximised. Absorption by the transcellular route diminishes in the more distal colon, a fact which has implications for delayed or sustained r elease formulations.