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

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A R Beaubien1, E Ormsby, A Bayne

  • 1Drug Toxicology Division, Health Protection Branch, Ottawa, Ontario, Canada.

Antimicrobial Agents and Chemotherapy
|June 1, 1991
PubMed

Insights

Aminoglycoside antibiotic ototoxicity in guinea pigs is linked to the total exposure time in the inner ear fluid, not peak concentration levels. This finding helps understand antibiotic-induced hearing loss.

Area of Science:

  • Ototoxicology
  • Pharmacokinetics
  • Auditory Neuroscience

Background:

  • Ototoxicity from aminoglycoside antibiotics is a significant clinical concern.
  • Previous research has not definitively linked perilymph concentrations to aminoglycoside-induced ototoxicity.

Purpose of the Study:

  • To investigate the relationship between amikacin levels in perilymph and ototoxicity.
  • To determine if perilymph concentration, rather than total exposure, drives amikacin ototoxicity.

Main Methods:

  • Guinea pigs were exposed to continuous amikacin infusion at varying rates.
  • Perilymph and plasma amikacin concentrations were measured over time.
  • Ototoxicity was assessed at different dosing durations and rates.

Main Results:

  • Perilymph amikacin levels and perilymph/plasma ratios remained constant across dosing rates and durations.
  • Amikacin levels in plasma and perilymph showed a linear relationship with the dosing rate.
  • The total area under the concentration-time curve in perilymph did not differ between dosing rates for threshold or severe ototoxicity.

Conclusions:

  • Amikacin ototoxicity appears to be related to the integral of concentration over time in the perilymph, not the peak concentration.
  • The total exposure duration in the perilymph is a critical factor in aminoglycoside-induced ototoxicity.

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