Pharkacokinetics and pharmacodynamics of furosemide after direct administration into the stomach or duodenum
✍ Scribed by Woo I. Lee; Woo H. Yoon; Wan G. Shin; In S. Song; Myung G. Lee
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 180 KB
- Volume
- 18
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
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 concentration of furosemide was reached within 1 h in both routes of administration, and the peak concentration was higher in all four subjects after a direct administration into the duodenum than after an oral administration. Furosemide was absorbed considerably after a direct administration of Lasix into the duodenum; the values of the area under the plasma concentration±time curves of furosemide from time zero to 4 h (AUC 0±4 h , 93´6 versus 122 mg min mL 71 , p<0´123) and the cumulative amounts of the dose excreted in 8 h (10 600 versus 15 000 mg, p<0´0185) and 24 h (11 300 versus 15 400 mg, p<0´0192) urine as unchanged furosemide were signi®cantly higher after a direct administration 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 versus 1670 mg as expressed in terms of furosemide, p<0´0858) when compared to a direct administration into the duodenum, possibly due to the increased gastric ®rst-pass metabolism of furosemide. The 8 h urine output and 8 h urinary excretion of sodium did not increase signi®cantly after a direct administration of Lasix into the duodenum, despite the signi®cantly greater amount of the drug delivered to the active 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 values of maximally ecient urinary excretion rate of furosemide during the 8 h experimental period than after a direct administration into the duodenum.