CHARACTERISTICS OF INTESTINAL-ABSORPTION OF ADINAZOLAM AND IN-VIVO EVALUATION OF ORAL SUSTAINED-RELEASE TABLETS OF ADINAZOLAM IN BEAGLE DOGS

The characteristics of intestinal absorption of adinazolam in rats wer e investigated using an in situ intestinal loop method on the upper, m iddle and lower parts of the small intestine, and colon. The disappear ance of the drug from the intestinal lumen was measured to estimate th e absorption. Adinazolam was readily absorbed from various sites of th e small intestine and colon indicating no absorption site specificity. Absorption followed first-order kinetics with a disappearance half-li fe of less than 15 min. Dose dependency or saturation of the absorptio n were not observed in the experimental concentration range of 5-1000 mug/ml. In one of the experiments to investigate the effect of postpra ndial administration, the intestinal absorption of adinazolam decrease d somewhat when the administered solution contained either 5% bile pow der or 5% polysorbate 80. In the biopharmaceutic study, the sustained release (SR) tablet significantly prolonged the plasma adinazolam conc entration in beagle dogs in comparison to that of the rapidly disinteg rating conventional tablets (conventional tablet) of adinazolam. The m ean residence time (MRT) of adinazolam from the SR tablets was about 5 -times greater than that of the conventional tablets.