Summary

A randomized four-way crossover study was carried out in 12 healthy volunteers to investigate the pharmacokinetics of a new oral combination of frusemide (40 mg) and amiloride (5 mg), formulated as a single tablet. The experimental design of this bioequivalence study used commercially-available 40 mg frusemide tablets and 5 mg amiloride tablets as reference drugs, administered either separately or concomitantly. From a statistical analysis of plasma levels of frusemide and amiloride, no significant differences between the reference drugs alone and the combination tablet were seen in peak plasma levels, mean times to peak or mean areas under the plasma concentration-time curves (AUCs). The ratio of AUCs of the combination tablet to the reference drugs approached a limiting value many hours prior to complete elimination of the drug and hence reliable bioavailability comparisons were possible with blood sampling up to 24 hours post-dose.