Pharmacokinetics of an oral frusemide/amiloride Combination tablet

Abstract

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.

Analytical HPLC Method Validation of Amiloride and Its Pharmacokinetic Study in Humans

“…Several studies have reported that peak plasma levels occur 4 hr after oral administration, absorption ranges from 90% to 95% of the dose and half-life ranges from 10-14 hr. [2][3][4][5] Since amiloride exhibits an extremely low therapeutic range (0.5-25 ng/mL), only a few sufficiently specific and sensitive HPLC methods for pharmacokinetic studies have been described. [6][7][8][9][10][11] The pharmacokinetics and bioavailability of amiloride in plasma and/or urine have been investigated by determining its levels by fluorometric, 12 radioactive, 13 densitofluorimetric, 14 or spectrometric 15 assays.…”

A high-throughput BIA-MPA method for the simultaneous determination of amiloride and furosemide

“…5 Furthermore, this combination is more effective for long-term treatment, since FMD has rapid absorption [6][7][8][9][10] and the presence of AMD (slower absorption) increases the length of time that the therapeutic effects last. 7,[11][12][13] A considerable number of analytical methods have been reported in the literature for the simultaneous determination of AMD and FMD, including digital derivative spectrophotometry, 3 spectrophotometry with partial least squares regression, 14 high-performance liquid chromatography with uorescence 4,5 or UV 5,[15][16][17] detection, capillary isotachophoresis, 18,19 micellar liquid chromatography with uorimetric detection, 20 solid-phase extraction followed by spectrouorimetry 1,2 and gas chromatography with electron impact mass spectrometry. 21 However, most of these methods have limitations, such as high cost, low throughput, and/or the need for laborious sample pre-treatment steps prior to analysis.…”