Quantitative relationships of the ototoxic interaction of kanamycin and ethacrynic acid.

We determined the range of doses of kanamycin sulfate and ethacrynic acid that results in an ototoxic interaction in guinea pigs. In addition, we determined the time interval between the administration of the two drugs that is needed to produce this interaction. In all cases, the magnitude of the ototoxic lesion was determined by measuring the cochlea's ability to generate both the sensitivity and intensity functions of the ac cochlear potential. In addition, the cochlear pathologic conditions, as determined by counting the number of missing hair cells in the organ of Corti, was found to correlate highly with the ac cochlear potential data. The dosage range of ethacrynic acid during which the interaction occurs is very narrow, while the dose range of kanamycin is very large.