Comparative acute cochlear toxicity of intravenous @entity11623 and XXXX in the purebred beagle.

@entity2167 @entity308 @entity1483 @entity11623
Comparisons were made of the effects of various doses of intravenous @entity11623 and @entity1483 on the primary auditory afferent activity (N1) and cochlear microphonics (CM) of beagles. The dose-response relationships of the N1 @entity308 to @entity11623 and @entity1483 are parallel; those of the @entity308 are also parallel but have a much shallower slope than those of the N1 @entity308 . With both drugs, N1 @entity308 occurs at lower doses than does @entity308 . The N1 @entity308 produced by a particular dose of @entity11623 or @entity1483 bore a linear relationship to the @entity308 produced. This finding supports the postulate that the cochlear site and mechanism of @entity2167 action of the loop diuretics are directed at an earlier step of the cochlear transduction process than N1. Using N1 @entity308 as the gross electrophysiologic index of @entity2167 , the acute @entity2167 potency of @entity11623 in beagles is approximately 6.5 times that of @entity1483 , whereas its diuretic potency is 40 to 60 times that of @entity1483 . Therefore, when clinical dosages of the two drugs are considered, the relative acute @entity2167 potency of @entity11623 in the beagle is 0.11 to 0.16 that of @entity1483 . This range is identical to the relative @entity2167 potency of 0.11 to 0.16 previously obtained in the cat. Serum concentrations of @entity11623 and @entity1483 increased 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 less than the mathematically predicted values. Histologic (light-microscopic) examination of the cochleas did not reveal any significant pathology.
