Rate of transport of ototoxic drugs into perilymph

By measuring concentration of kanamycin in perilymph after multiple doses, the accumulation of kanamycin in perilymph was observed. When the correlation between the concentration of kanamycin in perilymph and hair cell damage (by surface preparation technique) was pursued, a dose‐related phenomenon was observed. Furosemide levels have been measured in chinchilla body fluids after 100 mg/kg intravenous injection. The drug has a much longer half‐life in perilymph compared to other body fluid compartments. However, when this same dose is given to animals who had received 25 mg/kg injections every twelve hours for ten doses, no evidence of accumulation in any body fluids was noted. Changes in endocochlear potential (EP) in chinchillas receiving a single IV dose of furosemide 25, 50, of 100 mg/kg showed dose‐dependent changes. The time after administration of drug to initiation of EP recovery was 6, 9, and 19 min for these doses, respectively. The perilymph level of furosemide is 5 μg/ml at the time that recovery of EP is beginning after the 100 mg/kg IV dose. This may represent a threshold level for this drug. These studies support the existence of a blood labyrinth barrier with selective permeability. Kanamycin tends to accumulate in perilymph but furosemide does not. The mechanism underlying these differences in drug accumulation may be a differential toxic effect on membrane permeability or excretion rate from the perilymphatic space. This basic information helps to understand the differences of degree of hearing loss (permanent or temporary) observed in patients receiving antibiotics or diuretics.