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Pharkacokinetics and pharmacodynamics of furosemide after direct administration into the stomach or duodenum
Author(s) -
Lee Woo I.,
Yoon Woo H.,
Shin Wan G.,
Song In S.,
Lee Myung G.
Publication year - 1997
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(199712)18:9<753::aid-bdd63>3.0.co;2-k
Subject(s) - furosemide , duodenum , oral administration , pharmacokinetics , medicine , urine , pharmacology , diuretic , pharmacodynamics , endocrinology
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 μg min mL −1 , p <0·123) and the cumulative amounts of the dose excreted in 8 h (10 600 versus 15 000 μg, p <0·0185) and 24 h (11 300 versus 15 400 μg, p <0·0192) urine as unchanged furosemide were significantly 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 μg 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 urine output and 8 h urinary excretion of sodium did not increase significantly after a direct administration of Lasix into the duodenum, despite the significantly 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 efficient urinary excretion rate of furosemide during the 8 h experimental period than after a direct administration into the duodenum. © 1997 John Wiley & Sons, Ltd.