A RESIDENCE-TIME DISTRIBUTION ANALYSIS OF THE HYDRODYNAMICS WITHIN THE INTESTINE IN MAN DURING A REGIONAL SINGLE-PASS PERFUSION WITH LOC-I-GUT - IN-VIVO PERMEABILITY ESTIMATION

The goal of this study was to determine the most appropriate hydrodyna mic model for the Loc-I-Gut in-vivo perfusion system. The general mixi ng-tank-in-series model, which can approximate single mixing tank and laminar and plug-flow hydrodynamics was fitted to the observed experim ental residence-time distribution curves for the non-absorbable marker [C-14]PEG 4000. The residence-time distribution analysis shows that t he hydrodynamics of the perfusion solution within the jejunal segment in man is well approximated by a model containing on average between 1 -2 mixing tanks in series. The solution is well mixed when using perfu sion rates of 2.0, 3.0 and 6.0 mL min(-1). The average mean residence time estimates from the fitted residence-time distribution were 12+/-7 .6, 15+/-4.2 and 7.7+/-4.6 min, respectively, at these three perfusion rates. The mean volumes of the segment (Vs) were 25+/-15, 45+/-12 and 46+/-27 mt, respectively. There were no statistical differences betwe en 2.0, 3.0 and 6.0 mt min(-1) in respect of the number of mixing tank s (n) and mean residence times. This residence-time distribution analy sis indicates that the luminal fluid in the Loc-I-Gut perfusion system is well-mixed, and that permeability calculations based on the well-m ixed assumption most closely approximate the actual local (average) me mbrane permeability within the perfused segment.