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Pharmacokinetics and pharmacodynamics of furosemide after direct administration into the stomach or duodenum.

Abstract：

: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 (AUC0-4 h, 93.6 versus 122 micrograms min mL-1, p < 0.123) and the cumulative amounts of the dose excreted in 8 h (10,600 versus 15,000 micrograms, p < 0.0185) and 24 h (11,300 versus 15,400 micrograms, 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 micrograms 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.

journal_name

Biopharm Drug Dispos

journal_title

Biopharmaceutics & drug disposition

authors

Lee WI,Yoon WH,Shin WG,Song IS,Lee MG

doi

10.1002/(sici)1099-081x(199712)18:9<753::aid-bdd63

subject

Has Abstract

pub_date

1997-12-01 00:00:00

pages

753-67

issue

9

eissn

0142-2782

issn

1099-081X

pii

10.1002/(SICI)1099-081X(199712)18:9<753::AID-BDD63

journal_volume

18

pub_type

临床试验,杂志文章

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