PHARMACOKINETICS AND PHARMACODYNAMICS OF FUROSEMIDE AFTER DIRECT ADMINISTRATION INTO THE STOMACH OR DUODENUM

The pharmacokinetics and pharmacodynamics of furosemide were compared after an oral administration or a direct administration of Lasix into the duodenum in humans (40 mg). Furosemide was absorbed quickly after a direct administration of Lasix into the duodenum; the peak plasma co ncentration of furosemide was reached within 1 h in both routes of adm inistration, and the peak concentration was higher in all four subject s after a direct administration into the duodenum than after an oral a dministration. Furosemide was absorbed considerably after a direct adm inistration of Lasix into the duodenum; the values of the area under t he plasma concentration-time curves of furosemide from time zero to 4 h (AUC(0-4h), 93.6 versus 122 mu g min mL(-1), p < 0.123) and the cumu lative amounts of the dose excreted in 8 h (10 600 versus 15 000 mu g, p < 0.0185) and 24 h (11 300 versus 15 400 mu g, p < 0.0192) urine as unchanged furosemide were significantly higher after a direct adminis tration into the duodenum than after an oral administration. However, the amounts excreted in urine as glucuronide conjugates, a metabolite of furosemide, tended to increase after an oral administration (4030 v ersus 1670 mu g as expressed in terms of furosemide, p < 0.0858) when compared to a direct administration into the duodenum, possibly due to the increased gastric first-pass metabolism of furosemide. The 8 h ur ine output and 8 h urinary excretion of sodium did not increase signif icantly after a direct administration of Lasix into the duodenum, desp ite the significantly greater amount of the drug delivered to the acti ve site after a direct administration into the duodenum. This could be explained by the fact that the urinary excretion rates of furosemide after a direct administration into the stomach were closer to the valu es of maximally efficient urinary excretion rate of furosemide during the 8 h experimental period than after a direct administration into th e duodenum. (C) 1997 John Wiley & Sons, Ltd.