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, the AUC(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 AUC(0-->8 h) values of bumetanide after intraduodenal instillation were significantly smaller than AUC values after intraportal infusion at 10 (89.8 vs 569 microg min per ml) and 20 (304 vs 1230 microg 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.