Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Pharmacodynamic modeling of furosemide tolerance after multiple intravenous administration

Pharmacodynamic modeling of furosemide tolerance after multiple intravenous administration PHARMACODYNAMICS AND DRUG ACTION Pharmacodynamic modeling of furosemide tolerance after multiple intravenous administration Objective: Physiologic indirect-response models have been proposed to account for the pharmacodynamics of drugs with an indirect mechanism of action, such as fitrosemide. However, they have not been applied to tolerance development. The aim of this study was to investigate the development of tolerance after multiple intravenous dosing of furosemide in healthy volunteers. Methods: Three repetitive doses of 30 mg furosemide were given as rapid intravenous infusions at 0,4, and 8 hours to eight healthy volunteers. Urine samples were collected for a period up to 14 hours after the first dose. Volume and sodium losses were isovolumetrically replaced with an oral rehydration fluid. Results: Tolerance was demonstrated as a significant decrease in diuretic and natriuretic response over time. Total mean diuresis was 35% lower (p < 0.01) and total mean natriuresis was 52% lower (p < 0.0001) after the third dose of furosemide compared with the fnst dose. However, there were considerable interindividual variations in the rate and extent of tolerance development for both diuresis and natriuresis. Pharmacokinetic- pharmacodynamic modeling of tolerance development was performed with use of an indirect-response model with an additional “modifier” compartment. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Pharmacology & Therapeutics Wiley

Pharmacodynamic modeling of furosemide tolerance after multiple intravenous administration

Download PDF
14 pages

Loading next page...
 
/lp/wiley/pharmacodynamic-modeling-of-furosemide-tolerance-after-multiple-GqNYNE004x

References (25)

Publisher
Wiley
Copyright
© 1996 American Society for Clinical Pharmacology and Therapeutics
ISSN
0009-9236
eISSN
1532-6535
DOI
10.1016/S0009-9236(96)90170-8
Publisher site
See Article on Publisher Site

Abstract

PHARMACODYNAMICS AND DRUG ACTION Pharmacodynamic modeling of furosemide tolerance after multiple intravenous administration Objective: Physiologic indirect-response models have been proposed to account for the pharmacodynamics of drugs with an indirect mechanism of action, such as fitrosemide. However, they have not been applied to tolerance development. The aim of this study was to investigate the development of tolerance after multiple intravenous dosing of furosemide in healthy volunteers. Methods: Three repetitive doses of 30 mg furosemide were given as rapid intravenous infusions at 0,4, and 8 hours to eight healthy volunteers. Urine samples were collected for a period up to 14 hours after the first dose. Volume and sodium losses were isovolumetrically replaced with an oral rehydration fluid. Results: Tolerance was demonstrated as a significant decrease in diuretic and natriuretic response over time. Total mean diuresis was 35% lower (p < 0.01) and total mean natriuresis was 52% lower (p < 0.0001) after the third dose of furosemide compared with the fnst dose. However, there were considerable interindividual variations in the rate and extent of tolerance development for both diuresis and natriuresis. Pharmacokinetic- pharmacodynamic modeling of tolerance development was performed with use of an indirect-response model with an additional “modifier” compartment.

Journal

Clinical Pharmacology & Therapeutics – Wiley

Published: Jul 1, 1996

There are no references for this article.