No abstract

The ototoxicity of bumetanide and furosemide was compared in Topeka strain guinea pigs pretreated with kanamycin. The animals, anesthetized with pentobarbital, received a single dose of 400 mg/kg kanamycin subcutaneously and the diuretics via indwelling catheter in the jugular vein 2 hours later. Ototoxic drug effects were determined by measuring the electrophysiological responses of the cochlea to sound stimuli and by determining the presence or absence of cochlear sensory hair cells from the organ of Corti. Both bumetanide and furosemide produced permanent alteration of cochlear activity in the kanamycin-pretreated animals. The ototoxic effect of bumetanide is five times that of furosemide on a milligram-for-milligram basis. The ototoxic potential of bumetanide is one eighth that of furosemide when the doses are adjusted for diuretic potency difference between the two diuretics.

No abstract

Kanamycin was administered in total daily doses of 0 (vehicle), 100, 200 or 300 mg/kg to different groups of guinea pigs for two weeks. These total daily doses were administered according to three different dosing schedules, either as a single injection given once a day, divided into two equal doses and given twice a day, or divided into four equal doses and administered four times a day. It was found that the magnitude of the ototoxicity resulting from kanamycin administration was related to the total daily dose alone and not the dosing schedule. This lack of relationship between the dosing schedule and the magnitude of the ototoxicity due to kanamycin is the reverse of that reported for the nephrotoxicity resulting from gentamicin, tobramycin and netilmicin.

The ototoxic interaction between the aminoglycoside antibiotics (streptomycin, kanamycin, etc.) and the loop-inhibiting diuretics (ethacrynic acid, furosemide and bumetanide) has been well documented. This interaction causes extensive destruction of the hair cells of the cochlea. Brummett et al. (1974) demonstrated that this interaction did not occur with the non-loop-inhibiting diuretics and kanamycin. The present study was undertaken to determine if antibiotics other than the aminoglycosides could produce the ototoxic interaction when combined with a loop-inhibiting diuretic. Three antibiotics-viomycin, capreomycin, and polymyxin B- when given with ethacrynic acid were found to produce cochlear hair cell damage that was similar to that produced by aminoglycoside antibiotics administered with ethacrynic acid. Therefore, the interaction appears to be specific to the loop-inhibiting diuretics but not specific for the aminoglycoside antibiotics.