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It has been reported that even the administration of a single dose of kanamycin (KM), when used concurrently with furosemide (FM), could produce a severe permanent hearing loss after recovery of the temporary hearing loss due to FM. In order to investigate the hearing impairment caused by the combined administration of KM and FM, the effects of KM and FM on hearing impairment were examined various time intervals.The ototoxicity of cisplatin (CP) has been reported and the hearing loss caused by a single administration of CP and the effects of the combined administration of CP and FM were also studied.Using Hartley guinea pigs, the auditory brainstem response (ABR) was recorded to study the physiological changes and the morphological changes were observed by scanning and transmission electron microscopy. The KM concentrations in serum and perilymph were measured, and the following results were obtained.Subsequent to an intramuscular injection of KM (400rng/kg), FM (80mg/kg) was administered intravenously at various intervals of administration. The ABR study revealed that the most severe bearing loss at the administration intervals ranging from 30 minutes to 2 hours, whereas almost no combined effects were observed in ABR when the intervals were more than 3-4 hours.When an intravenous injection of KM (200mg/kg) was followed by intravenous injection of FM (80rng/kg), ABR disappeared in two days in the cases within intervals of 1 hour, and permanent hearing loss occurred.In cases administered CP 2mg/kg/day eight times or 4mg/kg/day four times, the ABR disappeared or the amplitude of ABR decreased obviously, as well as a severe degeneration of hair cells. The ABR began to return in some animals after withdrawal of the drug.When FM (80mg/kg) was intravenously administered 30-90 minutes after intramuscular injection of CP (4mg/kg or 6mg/kg), disappearance of ABR or decrease of amplitude was observed in two days, however ABR tended to recover thereafter in many cases. Morphologically significant destruction of hair cells was observed, but the changes of stria vascularis were slight.Hearing impairment caused by a combined medication of KM or CP with FM was found to be largely dependent on the intervals. It is suggested that the administration of FM during the high concentration of KM or CP in the blood may cause a temporary functional disturbance of the blood-cochlear barrier, which in turn causes KM or CP to be transferred in large quantities into the inner ear.

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[Sensorineural hearing impairment by combined administration of aminoglycoside drugs, loop diuretics and an anticancer drug (cisplatin)--an experimental study].