title: Furosemide pharmacokinetics and pharmacodynamics following gastroretentive dosage form administration to healthy volunteers.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120, Israel.
authors.forename: Eytan A
authors.initials: EA
authors.lastname: Klausner
authors.forename: Eran
authors.initials: E
authors.lastname: Lavy
authors.forename: David
authors.initials: D
authors.lastname: Stepensky
authors.forename: Eva
authors.initials: E
authors.lastname: Cserepes
authors.forename: Miklos
authors.initials: M
authors.lastname: Barta
authors.forename: Michael
authors.initials: M
authors.lastname: Friedman
authors.forename: Amnon
authors.initials: A
authors.lastname: Hoffman
mesh_terms: 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
chemical_list: D003692:Delayed-Action Preparations; D004232:Diuretics; D005665:Furosemide; D012964:Sodium