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Combination of long‐acting furosemide and instant‐acting amiloride: pharmacokinetics and pharmacodynamics in human subjects
Author(s) -
Flouvat B.,
Roux A.,
Leneveu A.,
Prinseau J.,
Alexandre JA
Publication year - 1991
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1991.tb00762.x
Subject(s) - pharmacodynamics , pharmacokinetics , pharmacology , furosemide , amiloride , medicine , chemistry , sodium , organic chemistry
Summary— The pharmacokinetics and pharmacodynamics of the combination of amiloride (2 times 2.5 mg) and long‐acting furosemide (2 times 10 mg) were compared with amiloride (5 mg) and furosemide (20 mg) in 12 healthy male volunteers aged 26.2 ± 1.6 years and weighing 68.8 ± 6.2 kg, after random order administration. Furosemide and amiloride plasma or urine concentrations were determined by HPLC with fluorimetric detection. The rate of absorption ( t max = 3 h) and the bioavailability of the two diuretics were not significantly modified by their combination. Furosemide plasma half‐life was 2.77 ± 1.04 h after the combination treatment and 2.76 ± 0.98 h alone, amiloride plasma half‐life was respectively 15.7 ± 4.6 h and 14.6 ± 3.7 h. The urinary elimination of furosemide was significantly higher in the 2–4 h interval in the combination treatment, accompanying its delayed maximum effect of diuresis. A synergistic effect was observed after the combination administration of the two diuretics; between the 2nd and the 8th hour, the sodium elimination was significantly increased ( P < 0.01) and the potassium excretion was significantly decreased ( P = 0.05). After a single dose, no modification of plasma or erythrocyte magnesium levels was observed. This study shows that the combination of the two drugs entails a synergy of their activities which does not involve pharmacokinetic changes.