Potentiation and Its Mechanism of Cochlear Damage Resulting from Furosemide and Aminoglycoside Antibiotics

Abstract

The severe ototoxic interaction of the combined administration of furosemide and aminoglycoside antibiotics (kanamycin, streptomycin and gentamicin) was studied in rabbits, and its mechanism clarified. Severe damage occurred not only in the inner ear but also in the kidney when both furosemide and aminoglycoside antibiotics were administered to rabbits. Kanamycin concentration after a single injection of kanamycin with furosemide was much higher not only in the perilymph but also in the cerebrospinal fluid and serum than that after a single injection of kanamycin alone. The ototoxic interaction following the combined use of furosemide and aminoglycoside antibiotics seems to be caused mainly by the inhibitory effect of furosemide on the excretion of aminoglycoside antibiotics from the kidneys.

Deafness Induction in Mice

“…The addition of a loop diuretic to an aminoglycoside administration has a more than additive ototoxic effect because diuretics facilitate aminoglycosides to pass the blood-cochlea barrier (3Y5); they allow aminoglycosides to more effectively spread through the cochlea by altering the endolymphatic potential (6,7), and they decrease the renal kanamycin clearance (8).…”

Effect of furosemide on aminoglycoside-induced nephrotoxicity and auditory toxicity in humans

“…This was the only patient we treated who developed sudden deafness and the only patient who received concurrent ethacrynic acid. DISCUSSION The data we 15 and 25%, respectively. Because these data were gathered in prospective, controlled, randomized, doubleblind trials, bias in assessing renal and auditory function was minimized.…”

“…A dose of 50 mg of furosemide per kg produced a minimal effect, whereas doses greater than 100 mg/kg produced severe irreversible decreases in cochlear potential. Obtani et al studied the interaction with kanamycin in rabbits given 30 mg offurosemide per kg for 5 to 60 days (15). All animals given the combination developed severe renal failure and severe loss of outer hair cells in the cochlea.…”

“…In experimental animals, administration of furosemide increases the nephrotoxicity and auditory toxicity of aminoglycosides (1,4,10,13,15,16,23). Only one clinical study evaluating aminoglycoside-induced nephrotoxicity has found that furosemide increases renal damage, whereas two studies have failed to find an interaction.…”

Interaction of Bumetanide and Kanamycin

“…Our previous study (Ohtani et al, 1978) has shown severe damage not only of the inner ear but also of the kidneys following the administration of both FM and aminoglycoside antibiotics to rabbits. The present study was undertaken to assess the ototoxic effect of the combined administration of KM and BUN in comparison with that of the combined FM-KM administration, employing BUN doses as low as 1/40 to 1/60 of the dose of FM in the previous study, hence on a diuretically equipotent basis.…”