Ototoxicity of neomycin and its penetration through the round window membrane into the perilymph

The ototoxicity of neomycin and its concentration in the perilymph after direct application on the round window membrane were studied. After placing 5 mg of neomycin on the round window membrane of guinea pigs for various time intervals, concentration of the drug in the perilymph was determined by high performance liquid chromatography, and the cochlea was examined by light microscopy. Neomycin penetrated the round window membrane quite easily, and its concentration in the perilymph became extremely high in a short time and then decreased gradually. This indicates that high concentration of neomycin in the perilymph can be attained by application of a small amount of the drug on the round window membrane. Ototoxicity of neomycin was observed after application for 4 hours. Cochlear damage increased as neomycin application time became longer, but no consistent relationship was noted between the concentration of neomycin and the amount of damage. This result is discussed from the point of concentration and persistence of the drug in the inner ear fluids.