The influence of frusemide formulation on diuretic effect and efficiency

Aims Changes in drug delivery rate may result in clinically important chang es in drug effects. For the loop diuretic frusemide, it would be desirable to develop controlled release preparations, that could maintain an effectiv e urinary excretion rate over a prolonged period of time. The aim of this s tudy 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 contro lled release formulations in a single-dose, double-blind, randomized 4-way cross-over design. The formulations were three study drugs with different e xtended dissolution rates (ER1(Tab), ER2(Tab) and ER3(Caps)) and one refere nce drug (LR). Urinary volume and contents of frusemide in urine were measu red in samples collected over 24 h. Results Substantial differences in frusemide recovery and diuretic efficien cy were observed between LR and all other formulations. At 24 h, mean total frusemide recoveries of ER1(Tab), ER2(Tab) and ER3(Caps) were 52%, 36% and 57% lower, respectively, compared with LR (P<0.01). Also at 24 h, mean tot al diuretic efficiency for ER1(Tab), ER2(Tab) and ER3(Caps) was 83%, 31% an d 135% higher, respectively, compared to LR. The rapid dissolution and abso rption of LR resulted in a high diuretic response from 0 to 3 h after dosin g. 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 ext ended rate of dissolution lead to a more prolonged absorption and subsequen t diuresis, but still maintain a similar cumulative response, due to their higher diuretic efficiency.