A MULTILOOP IN-SITU TECHNIQUE TO STUDY INTESTINAL DRUG ABSORPTION

A multi-loop in situ technique to study intestinal drug absorption has been developed using the rabbit as the animal model. Four segments, o ne each of the duodenum, the jejunum, the ileum, and the colon, are se lected and ligated. The corresponding mesenteric veins are cannulated. Drug is simultaneously administered to the four segments, intralumina lly. Mesenteric blood samples are collected continuously throughout th e experiment, after which the animal is euthanized. The segments are t hen isolated and homogenized, and the unabsorbed drug retained within the intestinal lumen is quantitated. The technique offers the followin g advantages over the contemporary techniques utilizing in vitro isola ted gut segments, in situ luminal perfusions as well as in vivo chroni cally isolated intestinal loops : (i) the tissue viability is extended by maintaining the blood circulation and the intestine intact ; (ii) the appearance of drug in the mesenteric blood can be monitored, inste ad of the disappearance of drug from the intestinal lumen ; (iii) the depressant effect of anaesthesia on intestinal motility, and consequen tly on uniform luminal fluid mixing, has been overcome ; (iv) as a res ult of the mixing, the entire surface area of the intestinal segments is exposed to the drug ; and (v) site-dependence, as well as the effec t of variation in input conditions, can be simultaneously examined.