Combination of long-acting furosemide and instant-acting amiloride: pharmacokinetics and pharmacodynamics in human subjects.
The pharmacokinetics and pharmacodynamics of the combination of amiloride (2 x 2.5 mg) and long-acting furosemide (2 x 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 (tmax = 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 less than 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.
Flouvat
B
B
Laboratoire de toxicologie et de pharmacocinétique, Hôpital Ambroise-Paré, Boulogne-Billancourt, France.
Roux
A
A
Leneveu
A
A
Prinseau
J
J
Alexandre
J A
JA
D000328:Adult; D000584:Amiloride / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000704:Analysis of Variance; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004231:Diuresis / Q000187:drug effects; D004338:Drug Combinations; D004357:Drug Synergism; D005665:Furosemide / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D008274:Magnesium / Q000097:blood; D008297:Male; D011188:Potassium / Q000097:blood / Q000652:urine; D011897:Random Allocation; D012964:Sodium / Q000097:blood / Q000652:urine
D004338:Drug Combinations; D000584:Amiloride; D005665:Furosemide; D012964:Sodium; D008274:Magnesium; D011188:Potassium