Furosemide pharmacokinetics and pharmacodynamics following gastroretentive dosage form administration to healthy volunteers.
The objective of this study was to evaluate the pharmacokinetic and pharmacodynamic properties of furosemide following gastroretentive dosage from (GRDF) administration. A furosemide (60 mg) GRDF, releasing the drug during 6 hours in vitro, or an immediate-release tablet was administered to healthy male volunteers (N = 14) in a crossover design. Food and liquid intake were standardized; urine was collected, weighed, and assayed for furosemide and sodium concentrations. Pharmacokinetics of furosemide following the GRDF administration, as compared to the tablet, showed lower Cmax and indicated a prolonged absorption phase leading to longer mean residence time in the stomach. The sustained input of the drug significantly improved diuretic and natriuretic efficiencies during the first 5 hours and thereby increased the total effects measured over 24 hours. The unfolding controlled-release GRDF of furosemide improved the pharmacodynamic actions due to the sustained absorption in the stomach and jejunum, which delayed the body's counteractivity to the drug effect.
Klausner
Eytan A
EA
Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120, Israel.
Lavy
Eran
E
Stepensky
David
D
Cserepes
Eva
E
Barta
Miklos
M
Friedman
Michael
M
Hoffman
Amnon
A
D000328:Adult; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005665:Furosemide / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D012964:Sodium / Q000652:urine
D003692:Delayed-Action Preparations; D004232:Diuretics; D005665:Furosemide; D012964:Sodium