Comparative ototoxicities of gentamicin and netilmicin in three model systems.
The ototoxic potentials of netilmicin and gentamicin were compared in three models: the standard in-vivo animal model (guinea pig), organ culture of the embryonic inner ear (mouse), and perilymphatic perfusions (guinea pig). Toxicity was assessed by light and electron microscopy of hair cells or by measurement of cochlear microphonic potentials. In vivo, netilmicin did not have any significant morphologic effect on hair cells under conditions (dose X duration) where gentamicin caused excessive hair cell loss. In organ culture, concentrations of netilmicin had to be at least tenfold higher than those of gentamicin in order to produce comparable damage. In direct applications of the drugs to the cochlea by perilymphatic perfusion, similar effects on cochlear microphonics were seen when netilmicin concentrations were more than threefold higher than those of gentamicin. It is suggested that netilmicin ototoxicity observed in vivo is low because of lesser penetration into the inner ear and lower intrinsic toxicity.