Furosemide pharmacokinetics and pharmacodynamics following gastroretentive dosage form administration to healthy volunteers.

Author(s): Klausner EA, Lavy E, Stepensky D, Cserepes E, Barta M, Friedman M, Hoffman A

Affiliation(s): Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120, Israel.

Publication date & source: 2003-07, J Clin Pharmacol., 43(7):711-20.

Publication type: Clinical Trial; Randomized Controlled Trial

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.