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The in vitro release of bumetanide from macrogol suppositories with and without weak acids (citric acid and tartaric acid) was studied. The release of bumetanide was not affected when weak acids were added to the suppositories. The in vivo rectal absorption of bumetanide from the suppositories was evaluated in rabbits. The bioavailability (absolute), expressed as the ratio of the area under the plasma concentration-time curve (AUC) following oral administration of bumetanide, was 39% that of intravenous administration. The value in bumetanide following rectal administration of the suppositories without weak acids was 32%. Each absolute bioavailability following rectal administration of the suppositories with 5% citric acid and 5% tartaric acid was 52% and 42%, respectively. These values were significantly larger than those of rectal administration of the suppositories without weak acids. Particularly, the bioavailability following rectal administration of the suppositories containing citric acid was significantly different from even those of oral administration. The absorption rate constants of bumetanide from the suppositories with weak acids were significantly larger than those following oral administration. These results indicated the possibilities of the rectal route of administration of drugs which are weak organic acids and show low or variable bioavailability following oral administration.

Enhanced Absorption of Bumetanide from Suppositories Containing Weak Acids in Rabbits.