POTENTIATION OF COCHLEAR AND RENAL DAMAGE RESULTING FROM FUROSEMIDE AND AMINOGLYCOSIDE ANTIBIOTICS

Abstract

The purpose of this study is to make the precise observation of the severe ototoxic interaction following the long-term combined administration of furosemide, one of the new potent diuretics, and aminoglycoside antibiotics (kanamycin, streptomycin and gentamicin), and to make clear the mechanism of the ototoxic interaction using rabbits. In order to confirm the mechanism, the concentration of kanamycin in body fluids (inner ear perilymph, serum and cerebrospinal fluid) after single injection of kanamycin with or without furosemide is studied, and histopathological findings of the kidney with long-term administration of drugs are carried out. The results obtained are as follows.
1. Severe outer hair cell damage has been shown to occur in rabbits following the combined administration of furosemide and aminoglycoside antibiotics (kanamycin and streptomycin). At the doses used no damage of the outer hair cells was detectable with furosemide or aminoglycoside antibiotics alone.
2. The kanamycin concentration in each of above-mentioned fluids was very high in the group receiving furosemide and kanamycin as much as that in the group receiving kanamycin alone.
3. Histopathological examination of the kidneys showed severe tubular necrosis in rabbits that received both furosemide and aminoglycoside antibiotics compared with rabbits that received furosemide or aminoglycoside antibiotics alone.
4. The mechanism of the ototoxic interaction following combined administration of furosemide and aminoglycoside antibiotics was discussed from the antibiotic concentration in body fluids and from the renal histopathological points of view.
5. Severe damage occurred in not only the inner ears but also kidneys when both furosemide and aminoglycoside antibiotics were administered to rabbits in even small dosage. Therefore, the administration of both drugs may be dangerous in patients.