Evidence that amikacin ototoxicity is related to total perilymph area under the concentration-time curve regardless of concentration

Beaubien, A R; Ormsby, Eric; Bayne, Aaron; Carrier, Karen; Crossfield, G; Downes, Michael A.; Henri, R.; Hodgen, M.

doi:10.1128/aac.35.6.1070

Cited by 41 publications

(22 citation statements)

References 21 publications

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“…The auditory toxicity is associated with the concentration of AG in the inner ear (14). In this study, low-dose LPS injection was shown to enhance the accumulation of GTTR in cochlear but not in serum, which is congruent with the earlier finding that the ototoxicity was independent of plasma AG concentration (7).…”

supporting

confidence: 90%

Finding ways to solve or prevent aminoglycoside-induced ototoxicity?

Woo

2016

Ann. Transl. Med.

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supporting

confidence: 90%

Finding ways to solve or prevent aminoglycoside-induced ototoxicity?

Woo

2016

Ann. Transl. Med.

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“…The degree of aminoglycoside-induced hair cell death appears to be dependent on the degree of intracellular drug uptake, and both decrease along a baso-apical gradient in the cochlea (Beaubien et al, 1991;Hackney et al, 1990;Hiel et al, 1992a;Hiel et al, 1992b). Physiologically, the cationic aminoglycosides reversibly abolish the transduction current in hair cells, and are permeant blockers of the transduction channels (Kroese et al, 1989;Marcotti et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

et al. 2006

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Aminoglycoside uptake in the inner ear remains poorly understood. We subcutaneously injected a fluorescently-conjugated aminoglycoside, gentamicin-Texas Red (GTTR), to investigate the in vivo uptake of GTTR in the inner ear of several vertebrates, and in various murine sensory cells using confocal microscopy.In bullfrogs, GTTR uptake was prominent in mature hair cells, but not in immature hair cells. Avian hair cells accrued GTTR more rapidly at the base of the basilar papilla. GTTR was associated with the hair bundle; and, in guinea pigs and mice, somatic GTTR fluorescence was initially diffuse before punctate (endosomal) fluorescence could be observed. A baso-apical gradient of intracellular GTTR uptake in guinea pig cochleae could only be detected at early time points (<3 h). In 21−28 day mice, cochlear GTTR uptake was greatly reduced compared to guinea pigs, 6-day-old mice, or mice treated with ethacrynic acid. In mice, GTTR was also rapidly taken up, and retained, in the kidney, dorsal root and trigeminal ganglia. In linguinal and vibrissal tissues rapid GTTR uptake cleared over a period of several days.The preferential uptake of GTTR by mature saccular, and proximal hair cells resembles the pattern of aminoglycoside-induced hair cell death in bullfrogs and chicks. Differences in the degree of GTTR uptake in hair cells of different species suggests variation in serum levels, clearance rates from serum, and/or the developmental and functional integrity of the blood-labyrinth barrier. GTTR uptake by hair cells in vivo suggests that GTTR has potential to elucidate aminoglycoside transport mechanisms into the inner ear, and as a bio-tracer for in vivo pharmacokinetic studies.

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“…An animal study showed that concentration and duration of amikacin may cause HL by increasing perilymph amikacin levels. 13 The duration and dose of the amikacin have been suggested to influence toxicity. 14 A previous study however showed that aminoglycoside treatment for >5 days in the NICU was associated with HL in univariable, but not in multivariable analysis.…”

Section: Discussionmentioning

confidence: 99%