Intestinal first-pass effect of bumetanide in rats

The intestinal first-pass effect of bumetanide was investigated after intravenous and intraportal infusion, and intragastric and intraduodenal instillation of the drug to rats. The AUC(0-->8) (h) values of bumetanide after intragastric and intraduodenal instillation of the drug, 10 and 20 mg/kg, were significantly smaller than AUC values after intraportal administration, suggesting that the gastrointestinal first-pass effect of bumetanide was considerable in rats. However. thr AUG(0-->8 h) values of bumetanide between intragastric and intraduodenal instillation were comparable, suggesting that the gastric first-pass effect of bumetanide was almost negligible in rats. The AUG(0-->8) (h) values of bumetanide after intraduodenal instillation were significantly smaller than AUC values after intraportal infusion at 10 (89.8 vs 569 mu g min per ml) and 20 (304 vs 1230 mu g min per ml) mg/kg, indicating that the first-pass organ(s) of bumetanide was intestine. The F values were 15.8 and 24.7% after intraduodenal instillation of bumetanide, 10 and 20 mg/kg, respectively. Approximately 76.1 and 76.5% of intraduodenally instilled bumetanide disappeared (as a result of absorption and first-pass effect) after 10 and 20 mg/kg, respectively. Therefore, it could be concluded that approximately 60.3 and 51.8% of the oral dose of bumetanide disappeared by intestinal first-pass effect at 10 and 20 mg/kg, respectively. (C) 2000 Elsevier Science B.V. All rights reserved.