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 in 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 monitored by gamma scintigraphy. Beagles were used initially to demonstrate the functional utility of the device where a solution of ranitidine hydrochloride (150 mg) was non-invasively delivered to the stomach, proximal small intestine and distal small intestine. A subsequent first time in human study enrolled twelve healthy male volunteers where the intended site of release was the stomach, early small bowel, distal small bowel or colon.

RESULTS

Preliminary studies conducted in beagles indicated that the RDDC operated successfully and the onset of ranitidine serum levels were dependent 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 no 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 (range = 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 events. The prototype RDDC operated successfully in nine of the twelve human volunteers and the cause for the three failures was attributed to mechanical failure while the electronics assembly performed favorably.

CONCLUSIONS

This prototype remote control capsule was shown to be well tolerated and functional to use in human volunteers as well as beagles. The application of the device coupled with gamma scintigraphy has the potential to be a valuable and rapid method to non-invasively evaluate regional drug absorption in the gastrointestinal tract under conditions that are both pharmaceutically and physiologically meaningful.