INTERACTION OF BUMETANIDE AND KANAMYCIN

Abstract

The absolute diuretic potency of bumetanide (BUN) is 40-60 times that of furosemide (FM). When dosage of two drugs clinically used are considered, the relative ototoxic potency of BUN is very low (about 1/10 of FM). The purpose of this study was to determine the combined ototoxic effect of BUN with kanamycin (KM), and to compare it with that of FM and KM. Doses of BUN were 1/40 and 1/60 of FM. The results obtained were as follows.
1. Severe damage of the outer hair cell occurred in rabbits following the combined administra-tion of BUN and KM. No damage of the outer hair cells was detectable when BUN or KM were used alone with the same dose. The damage of the outer hair cells in rabbits injected with both BUN and KM was approximately equal to that of rabbits receiving both FM and KM. And there was no significant difference in the pattern of the outer hair cell damage between these rabbits.
2. The kidney of rabbits received both BUN and KM also showed the severely damaged lesions of the proximal tubules. And their lesions resembled that found in rabbits received both FM and KM. All of rabbits injected with BUN or KM alone showed the normal renalhistological findings under a light microscope.
Therefore, the ototoxicity of BUN in its clinical use is less than that of FM, but the ototoxic effect of BUN used with KM is approximately equal to that of FM with KM. That is, the combined ototoxic effect of the loop diuretics (BUN and FM) and KM may by closely related to the diuresis of diuretics. Severe damage occurred not only in the inner ear but also in the kidney when both BUN and KM were administered to rabbits. It may be, therefore, concluded that the combined administration of BUN and KM (probably another aminoglycoside antibiotics too) would also be dangerous to patients.