Comparative Acute Ototoxicity of Intravenous Bumetanide and Furosemide in the Pure-Bred Beagle
Document Type
Article
Publication Date
3-30-1979
Description
The effects of various doses of intravenous bumetanide and furosemide on the N1 and cochlear microphonics (CM) of beagles were determined in a quantitative (statistical) manner. Serum concentrations of these two "loop" diuretics were also determined at 3.5 min after the injections in the majority of the animals. The dose-response relationships of the N1 depressions to bumetanide and furosemide are parallel; those of the CM depressions are also parallel but have a much shallower slope than those of the N1 depressions. With both drugs, N1 depression occurs at lower doses than does CM depression. When multiple linear regression analysis is performed, the N1 depression produced by a particular dose of bumetanide or furosemide is found to bear a linear relationship to the CM depression produced. This finding supports the postulate that the cochlear site and mechanism of ototoxic action of the "loop" diuretics are directed at an earlier step of the cochlear transduction process than N1. Serum concentrations of bumetanide and furosemide increase linearly with the doses of the two drugs, except for the highest dose given (100 mg/kg for both drugs). The serum concentrations at that dose of both drugs are lower than the mathematically predicted values. Histological (light microscopic) examination of the cochleas did not reveal any significant pathological changes produced in the stria vascularis, outer and inner hair cells, afferent and efferent nerve terminals, or the spiral ganglia and efferent nerve bundles. Using N1 depression as the gross electrophysiologic index of ototoxicity, the acute ototoxic potency of bumetanide in beagles is approximately 6.5 times that of furosemide whereas its diuretic potency is 40-60 times that of furosemide. Therefore, when clinical dosages of the two drugs are considered, the relative, acute ototoxic potency of bumetanide in the beagle is 0.11-0.16 that of furosemide. This range is identical to the relative ototoxic potency of 0.11-0.16 previously obtained in the cat.
Citation Information
Don Brown, R.; Manno, Joseph E.; Daigneault, Ernest A.; and Manno, Barbara R.. 1979. Comparative Acute Ototoxicity of Intravenous Bumetanide and Furosemide in the Pure-Bred Beagle. Toxicology and Applied Pharmacology. Vol.48(1 PART 1). 157-169. https://doi.org/10.1016/S0041-008X(79)80018-6 PMID: 452038 ISSN: 0041-008X