Back to Journals » Drug Design, Development and Therapy » Volume 9

Randomized, open-label, blinded-endpoint, crossover, single-dose study to compare the pharmacodynamics of torasemide-PR 10 mg, torasemide-IR 10 mg, and furosemide-IR 40 mg, in patients with chronic heart failure

Authors Ballester MR, Roig E, Gich I, Puntes M, Delgadillo J, Santos B, Antonijoan RM

Received 8 April 2015

Accepted for publication 5 June 2015

Published 5 August 2015 Volume 2015:9 Pages 4291—4302


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 6

Editor who approved publication: Prof. Dr. Wei Duan

Maria Rosa Ballester,1,2 Eulàlia Roig,3,4 Ignasi Gich,1,2 Montse Puntes,1 Joaquín Delgadillo,2,5 Benjamín Santos,5 Rosa Maria Antonijoan1,2

1Drug Research Center (CIM), Biomedical Research Institute Sant Pau (IIB Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, 2Pharmacology and Therapeutics Department, Universitat Autònoma de Barcelona (UAB), Bellaterra, 3Cardiology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, 4Universitat Autònoma de Barcelona (UAB) Bellaterra, 5Scientific Area, Ferrer Internacional, SA, Spain

Purpose: Diuretics are the primary treatment for the management of chronic heart failure (HF) symptoms and for the improvement of acute HF symptoms. The rate of delivery to the site of action has been suggested to affect diuretic pharmacodynamics. The main objective of this clinical trial was to explore whether a prolonged release tablet formulation of torasemide (torasemide-PR) was more natriuretically efficient in patients with chronic HF compared to immediate-release furosemide (furosemide-IR) after a single-dose administration. Moreover, the pharmacokinetics of torasemide-PR, furosemide-IR, and torasemide-IR were assessed in chronic HF patients as well as urine pharmacodynamics.
Methods: Randomized, open-label, blinded-endpoint, crossover, and single-dose Phase I clinical trial with three experimental periods. Torasemide-PR and furosemide-IR were administered as a single dose in a crossover fashion for the first two periods, and torasemide-IR 10 mg was administered for the third period. Blood and urine samples were collected at fixed timepoints. The primary endpoint was the natriuretic efficiency after administration of torasemide-PR and furosemide-IR, defined as the ratio between the average drug-induced natriuresis and the average drug recovered in urine over 24 hours.
Results: Ten patients were included and nine completed the study. Here, we present the results from nine patients. Torasemide-PR was more natriuretically efficient than furosemide-IR (0.096±0.03 mmol/µg vs 0.015±0.0007 mmol/µg; P<0.0001). Mictional urgency was lower and more delayed with torasemide-PR than with furosemide-IR.
Conclusion: In a study with a limited sample size, our results suggest that 10 mg of torasemide-PR is more natriuretically efficient than 40 mg of furosemide-IR after single-dose administration in patients with chronic HF over a 24-hour collection period. Further studies are necessary to evaluate potential pharmacodynamic differences between torasemide formulations and to assess its impact on clinical therapeutics.

Keywords: torasemide, furosemide, controlled-release preparation, efficiency, heart failure, pharmacodynamics

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]