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Antimicrob Agents Chemother 1986 Jul;30(1):96-100
The kinetics of the entry of three aminoglycosides into inner-ear tissues of the guinea pig after acute and chronic administration were compared: gentamicin toxic to the cochlea and the vestibule, amikacin preferentially cochleotoxic, and netilmicin of low ototoxic liability. During constant intravenous infusion, levels of the three drugs in plasma tended to reach a plateau after 1 h, while levels in perilymph did not reach a plateau within 6 h. The drug concentrations in both vestibular and cochlear tissues quickly reached saturation. Amikacin and gentamicin concentrations were similar in vestibular and cochlear tissues, while netilmicin values were somewhat lower. After 1 week of chronic treatment (100 mg of drug per kg of body weight daily subcutaneously), levels of gentamicin and amikacin in tissue were similar to each other and were not significantly different between cochlear and vestibular tissues. Netilmicin concentrations again were somewhat lower in the tissues, but identical to those of the other drugs in the perilymph. After 3 weeks of treatment, all of the drugs were equally distributed in the inner-ear tissues. Release of the drug from the tissues after the 3-week treatment was faster for amikacin (83% decrease after 20 days) than for netilmicin and gentamicin (approximately 50% decrease). There was no correlation, under any of the experimental conditions, between the drug concentrations and their degrees of toxicity. These results demonstrate that selective aminoglycoside ototoxicity cannot be explained by a preferential uptake or accumulation of drugs in the afflicted tissues or in the perilymph.
PMID: 3489440, UI: 86321937
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