PHARMACOKINETICS AND URINARY ELECTROLYTE EXCRETION EFFECTS OF ORAL FRUSEMIDE AND FRUSEMIDE-AMILORIDE COMBINATION TABLETS IN HEALTHY-SUBJECTS

A randomized cross over study was carried out in 12 healthy volunteers to investigate simultaneously the pharmacokinetics and the effects on urinary volume and electrolyte excretion after administration of single doses of 40 mg frusemide and a combination tablet containing both 40 mg frusemide and 5 mg amiloride. From a statistical analysis of plasma levels of frusemide and amiloride measured by HPLC methodology, no significant difference between the reference drug alone, frusemide, and the combination tablets was observed in mean peak plasma levels, mean times to peak or mean areas under the plasma concentration-time curves (AUC). Frusemide and the combination tablet both produced a rapid and powerful diuresis in the 0-2 hours postdose period and did not differ significantly in urine output at any time point. However a difference in natriuretic activity was observed between frusemide and the combination with the latter producing a significantly greater sodium excretion in the 0 to 2 hours period (p < 0,05). Potassium retaining activity throughout the 24 hours was marked after the administration of the combination, the potassium excretion being significantly less (p < 0,05) than either control of frusemide alone. There was also a significant correlation between plasma levels of frusemide and the time course of urine and electrolyte excretion in healthy subjects.