Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
A. F. Parr, E. P. Sandefer, R. A. Casper, M. L. McCartney, C. J. McClain, U. Y. Ryo, and G. A. Digenis. Evaluation of a prototype remote drug delivery capsule (RDDC) in healthy adult volunteers for non-invasive regional drug absorption studies in the GI tract of man. Pharm. Res. 14:S-654 (1997).
M. C. Meyer, A. B. Straughn, R. M. Mhatre, V. P. Shah, R. L. Williams, and L. J. Lesko. Lack of in vivo/in vitro correlations for 50 mg and 250 mg primidone tablets. Pharm. Res. 15:1085–1089 (1998).
K. L. Audus, R. L. Bartel, I. J. Hidalgo, and R. T. Borchardt. The use of cultured epithelial and endothelial cells for drug transport and metabolism studies. Pharm. Res. 7:435–451 (1990).
P. Artursson and R. T. Borchardt. Intestinal drug absorption and metabolism in cell cultures: Caco-2 and beyond. Pharm. Res. 14:1655–1658 (1997).
M. F. Williams, G. E. Dukes, W. Heizer, Y. H. Han, D. J. Hermann, T. Lampkin, and L. J. Hak. Influence of gastrointestinal site of drug delivery on the absorption characteristics of ranitidine. Pharm. Res. 9:1190–1198 (1992).
W. H. Barr, E. M. Zola, E. L. Candler, S. M. Hwang, A. V. Tendolkar, R. Shamburek, B. Parker, and M. D. Hilty. Differential absorption of amoxicillin from the human small and large intestine. Clin. Pharm. Ther. 56:279–285 (1994).
T. Gramatte. Griseofulvin absorption from different segments in the human small intestine. Biopharm. Drug Disp. 15:747–759 (1994).
K. K. Chan, A. Buch, R. D. Glazer, V. A. John, and W. H. Barr. Site-differential gastrointestinal absorption of benazepril hydrochloride in healthy volunteers. Pharm. Res. 11:432–437 (1994).
T. Gramatte, R. Oertel, B. Terhaag, and W. Kirch. Direct demonstration of small intestinal secretion and site-dependent absorption of the beta-blocker talinolol in humans. Clin. Pharm. Ther. 59:541–549 (1996).
N. W. Read, M. N. Al Janabi, T. E. Bates, and D. C. Barber. Effect of gastrointestinal intubation on the passage of a solid meal through the stomach and small intestine in humans. Gastroenterology 84:1568–1572 (1983).
S. P. Eriksen, J. V. Swintosky, E. J. Serfass, T. H. Lin, J. Abrams, and F. M. Sturtevant. Equipment and methodology for relating gastrointestinal absorption to site of drug release. J. Pharm. Sci. 50:151–156 (1961).
E. T. Lin, J. R. Guarini, S. P. Eriksen, and J. V. Swintosky. Effect of the site of release on the absorption of Trimeprazine-S-35 and Penicillin G in Dogs. J. Pharm. Sci. 53:1357–1359 (1964).
A. Hemmati. Site of fat absorption in the intestinal tract: Studies using a remote control capsule and iodine-131 labelled fat. Verth. Dtsch. Ges. Inn. Med. 75:672–675 (1969).
B. Hugemann and O. Schuster. Vorrichtung zur freisetzung von substanzen an definierten orten des verdauungstraktes. Patent Application: Germany DE 2928477 C3 (A 61 K 9/00) (1982).
O. Schuster, B. Hugemann, E. H. Graul, and D. Loew. Absorption-slokalistion von furosemid durch verwendung einer ferngesteuerten arzneimittelkapsel unter röntgen-und CT-kontrolle. In: E. H. Graul, D. Loew, eds. Pathophysiologie und Therapie des gestörten Natrium-und Wasserhaushaltes, (Workshop Diuretika `84, Bad Nauheim, April 1984) 1984, pp. 128–137.
A. H. Staib, D. Loew, S. Harder, E. H. Graul, and R. Pfab. Measurement of theophylline absorption from different regions of the gastrointestinal tract using a remote controlled drug delivery device. Eur. J. Clin. Pharmacol. 30:691–697 (1986).
A. H. Staib, D. Beermann, S. Harder, U. Fuhr, and D. Liermann. Absorption differences of ciprofloxacin along the human gastrointestinal tract using a remote-control drug delivery device (HF capsule). Am. J. Med. 87:66s–69s (1989).
S. Harder, U. Fuhr, D. Beermann, and A. H. Staib. Ciprofloxacin absorption in different regions of the human gastrointestinal tract: Investigations with the HF capsule. Br. J. Clin. Pharmacol. 30:35–39 (1990).
U. Fuhr, A. H. Staib, S. Harder, K. Becker, D. Liermann, G. Schlollnhammer, and I. S. Roed. Absorption of ipsapirone along the human gastrointestinal tract. Br. J. Clin. Pharmacol. 38:83–86 (1994).
H. Bode, E. Brendel, G. Ahr, U. Fuhr, S. Harder, and A. H. Staib. Investigation of nifedipine absorption in different segments of the human gastrointestinal tract after simultaneous administration of C-13 and C-12 nifedipine. Eur. J. Clin. Pharmacol. 50:195–201 (1996).
G. A. Digenis and E. P. Sandefer. Gamma scintigraphy and neutron activation techniques in the in vivo assessment of orally administered dosage forms. Crit. Rev. Ther. Drug Carrier Sys. 7:309–345 (1991).
R. A. Casper, M. L. McCartney, W. J. Jochem, and A. F. Parr (1992): Medical capsule device actuated by radio-frequency (RF) signal. Patent Application: USA 5167626 and 5170801, 1 Dec 1992.
I. R. Wilding, A. J. Coupe, and S. S. Davis. The role of gamma scintigraphy in oral drug delivery. Adv. Drug Del. Rev. 7:87–117 (1991).
E. P. Sandefer and G. A. Digenis. A definitive method to evaluate enteric delivery systems targeting the proximal small intestine. 16th Pharmaceutical Technology Conference and Exhibition, Athens, Greece, April, 1997. Volume 2, pp. 46–69.
S. S. Davis, J. G. Hardy, and J. W. Fara. Transit of pharmaceutical dosage forms through the small intestine. Gut 27:886–892 (1986).
W. J. Doll, E. P. Sandefer, R. C. Page, U. Y. Ryo, D. R. Friend, D. L. Azarnoff, and G. A. Digenis. A bioavailability study of leuprolide acetate directly released in the ileum and colon of healthy human subjects using gamma scintigraphy and the Inteli-Site capsule. Pharm. Res. 14:S-654 (1997).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Parr, A.F., Sandefer, E.P., Wissel, P. et al. 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. Pharm Res 16, 266–271 (1999). https://doi.org/10.1023/A:1018884510163
Issue Date:
DOI: https://doi.org/10.1023/A:1018884510163