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Clinical Trial
. 1999 Sep;48(3):361-6.
doi: 10.1046/j.1365-2125.1999.00015.x.

The influence of frusemide formulation on diuretic effect and efficiency

M Wakelkamp  1 , A Blechert, M Eriksson, K Gjellan, C Graffner
Affiliations
Clinical Trial

The influence of frusemide formulation on diuretic effect and efficiency

M Wakelkamp et al. Br J Clin Pharmacol. 1999 Sep.

Abstract

Aims: Changes in drug delivery rate may result in clinically important changes in drug effects. For the loop diuretic frusemide, it would be desirable to develop controlled release preparations, that could maintain an effective urinary excretion rate over a prolonged period of time. The aim of this study was to investigate the influence of frusemide formulation on frusemide recovery, diuretic effect and efficiency.

Methods: Twelve subjects were given 60 mg of four different frusemide controlled release formulations in a single-dose, double-blind, randomized 4-way cross-over design. The formulations were three study drugs with different extended dissolution rates (ER1Tab, ER2Tab and ER3Caps ) and one reference drug (LR). Urinary volume and contents of frusemide in urine were measured in samples collected over 24 h.

Results: Substantial differences in frusemide recovery and diuretic efficiency were observed between LR and all other formulations. At 24 h, mean total frusemide recoveries of ER1Tab, ER2Tab and ER3Caps were 52%, 36% and 57% lower, respectively, compared with LR (P<0.01). Also at 24 h, mean total diuretic efficiency for ER1Tab, ER2Tab and ER3Caps was 83%, 31% and 135% higher, respectively, compared to LR. The rapid dissolution and absorption of LR resulted in a high diuretic response from 0 to 3 h after dosing. However, from 0 to 24 h, there were no differences in diuretic response between the formulations.

Conclusions: Controlled release formulations of frusemide with a low and extended rate of dissolution lead to a more prolonged absorption and subsequent diuresis, but still maintain a similar cumulative response, due to their higher diuretic efficiency.

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Figures

Figure 1
Figure 1
Mean (s.d.) in vitro dissolution profiles of ER1Tab (•), ER2Tab (▪), ER3Caps (○) and LR (▵).
Figure 2
Figure 2
Mean frusemide excretion rate (a), induced diuresis (b) and diuretic efficiency (c) vs time following the administration of ER1Tab (•), ER2Tab (▪), ER3Caps (○) and LR (▵).
Figure 3
Figure 3
Mean in vitro dissolution profiles of 15 batches of Lasix® Retard®.
See this image and copyright information in PMC

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