The relationship between the cytotoxicity of kanamycin and ethacrynic acid for mammalian cells in vitro and their ototoxicity in vivo.

Dose-effect curves for inhibition of growth of P388/P mouse lymphoma cells by ethacrynic acid and kanamycin used alone and in combination were determined in vitro. Ethacrynic acid was 600 times more potent than kanamycin and combinations of the drugs resulted in overall additive effects. These results were compared with known dose-effect data on the ototoxicity of these drugs in vivo. Kanamycin was highly selective in its toxicity for cochlear hair cells compared to cultured cells. The dose-effect data for ethacrynic acid was coincident with that reported for functional and biochemical effects on the cochlea following perilymphatic perfusion with the drug. The potentiation observed following the ototoxic interaction the two drugs in vivo was not observed following combinations of the drugs in vitro.