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The influence of frusemide formulation on diuretic effect and efficiency
M Wakelkamp1, A Blechert, M Eriksson
1Division of Clinical Pharmacology, Department of Medical Laboratory Sciences and Technology, Karolinska Institutet, Huddinge University Hospital, S-141 86 Huddinge, Sweden.
British Journal of Clinical Pharmacology
|October 6, 1999
Summary
Controlled release frusemide formulations offer prolonged absorption and diuresis. Despite lower initial recovery, these formulations demonstrate higher diuretic efficiency over 24 hours compared to immediate-release frusemide.
Area of Science:
- Pharmacology
- Drug Delivery Systems
- Clinical Pharmacy
Background:
- Drug delivery rate significantly impacts therapeutic effects, necessitating controlled-release formulations for sustained drug action.
- Frusemide (a loop diuretic) requires optimized formulations for prolonged effective urinary excretion.
- Investigating frusemide formulation effects on recovery, diuretic effect, and efficiency is crucial for therapeutic management.
Purpose of the Study:
- To evaluate the influence of different controlled-release frusemide formulations on drug recovery and diuretic response.
- To compare the diuretic efficiency of extended-release (ER) frusemide formulations against a reference immediate-release (LR) formulation.
- To determine the pharmacokinetic and pharmacodynamic profiles of novel frusemide formulations.
Main Methods:
- A double-blind, randomized 4-way cross-over study involving 12 subjects.
- Administration of 60 mg of four frusemide formulations: three extended-release (ER1Tab, ER2Tab, ER3Caps) and one immediate-release (LR).
- Collection and analysis of urine samples over 24 hours to measure volume and frusemide content.
Main Results:
- Significant differences in frusemide recovery and diuretic efficiency were observed between formulations.
- ER formulations showed substantially lower total frusemide recovery (52-57% less) compared to LR at 24 hours (P<0.01).
- ER formulations exhibited higher diuretic efficiency (31-135% more) than LR at 24 hours, despite similar overall diuretic response from 0-24 hours.
Conclusions:
- Extended-release frusemide formulations with slow dissolution rates promote prolonged absorption and diuresis.
- These controlled-release formulations achieve a similar cumulative diuretic response as immediate-release formulations due to enhanced diuretic efficiency.
- Optimized frusemide formulations can improve therapeutic outcomes by modulating drug delivery and diuretic response.