Comparison between rabbits and beagle dogs of sustained-release effect of gelatin microcapsules containing piretanide

Abstract

To use piretanide, a commercially available loop diuretic, as a long-acting antihypertensiue agent, we attempted to prepare it in sustained-release form by microencapsulation using gelatin. Gelatin microcapsules of piretanide were administered to rabbits and beagle dogs for pharmacokinetic evaluation, taking the gastrointestinal transit rate into consideration. Commercial piretanide tablets were used as control and treated in the same manner. The rate-determining steps were the gastrointestinal absorption process for the tablets and the drug-release process for the microcapsules in both animal species. Drug mobility in the gastrointestinal tract was considerably faster in dogs than in rabbits, but there was almost no difference between the two species in the amount of drug which remained unabsorbed in the gastrointestinal tract. As a result, gelatin microcapsules of piretanide showed satisfactory sustained-release properties in beagle dogs, although control of the drug release rate in rabbits could not be clearly evaluated.