Evaluation of the feasibility and use of a prototype remote drug delivery capsule (RDDC) for non-invasive regional drug absorption studies in the GI tract of man and beagle dog

Purpose. Evaluate a prototype Remote Drug Delivery Capsule (RDDC) For use i n beagle dogs and human volunteers For non-invasive drug absorption studies in different regions of the gastrointestinal tract. Methods. The device was dual radiolabeled and GI transit of the RDDC was mo nitored by gamma scintigraphy. Beagles were used initially to demonstrate t he functional utility of the device where a solution of ranitidine hydrochl oride (150 mg) was non-invasively delivered to the stomach, proximal small intestine and distal small intestine. A subsequent first time in human stud y enrolled twelve healthy male volunteers where the intended site of releas e was the stomach, early small bower, distal small bowel or colon. Results. Preliminary studies conducted in beagles indicated that the RDDC o perated successfully and the onset of ranitidine serum levels were dependen t on the time of capsule activation and site of drug release. Results from the human study showed that all twelve subjects swallowed the device with n o discomfort. Mean gastric emptying of the RDDC was 1.50 +/- 1.28 h (range = 0.25 to 4.25 h), and total small intestine transit was 4.79 +/- 1.82 h (r ange = 2.00 to 8.25 h). The capsule was retrieved from the feces at 30.25 /- 15.21 h (range = 14.12 to 74.25 h) and there were no reported adverse ev ents. The prototype RDDC operated successfully in nine of the twelve human volunteers and the cause for the three failures was attributed to mechanica l failure while the electronics assembly performed favorably. Conclusions, This prototype remote control capsule was shown to be well tol erated and functional to use in human volunteers as well as beagles. The ap plication of the device coupled with gamma scintigraphy has the potential t o be a valuable and rapid method to non-invasively evaluate regional drug a bsorption in the gastrointestinal tract under conditions that are both phar maceutically and physiologically meaningful.