REGIONAL JEJUNAL PERFUSION, A NEW INVIVO APPROACH TO STUDY ORAL-DRUG ABSORPTION IN MAN

Recently a new in vivo approach in man, using a regional intestinal perfusion technique. has been developed. The perfusion tube consists of a multichannel tube with two inflatable balloons, which are placed 10 cm apart. The tube is introduced orally and the time required for insertion and positioning of the tube is approximately 1 hr. In the present study eight healthy subjects were perfused in the proximal jejunum on three separate occasions. The first two perfusion experiments used the same flow rate, 3 ml/min, and the third experiment used 6 ml/min. Phenazone (antipyrine) was chosen as the model drug. The recovery of PEG 4000 in the outlet intestinal perfusate was complete in experiments 1 and 2, but slightly lower (90%) when the higher flow rate was used. The mean (+/- SD) fraction of phenazone absorbed calculated from perfusion data was 51 +/- 12% (3 ml/min), 64 +/- 19% (3 ml/min), and 42 +/- 27% (6 ml/min) for the three experiments, respectively. The mean fraction absorbed estimated by deconvolution of the plasma data was 47 +/- 16%, 51 +/- 19%, and 38 +/- 26%, respectively. The effective permeability of phenazone was 5.3 +/- 2.5, 11 +/- 6.8, and 11 +/- 12 (X 10(4)) cm/sec, respectively. We have shown that it was possible to establish a tight intestinal segment which behaved as a well-mixed compartment. The low perfusion rate of 3 ml/min was preferred, since it resulted in the lowest variability in absorption. The absorption ot' phenazone and d-glucose were highly correlated, which was due partly to the mean residence time of the solution in the intestinal segment, but other factors such as variable mucosal surface area also seemed to be important. The new per-fusion method was validated by the observed agreement found between absorption from the intestinal perfusate and the degree of absorption obtained by deconvolution of the plasma concentrations. Thus, the regional jejunal perfusion technique seems to have great potential for quantitative and mechanistic evaluations of drug absorption from the human intestine.