Inner ear changes with intracochlear gentamicin administration in Guinea pigs.
OBJECTIVE
Transtympanic administration of gentamicin is reported to be a useful treatment for vertigo in such conditions as Meniere's disease, and determining appropriate clinical dosage of gentamicin is difficult. The authors examined the relation between gentamicin dosages and inner ear function in guinea pigs.


METHODS
This study is a basic science project designed to examine cochlear and vestibular function in animal models.


METHODS
Various concentrations of gentamicin solution were infused into the right inner ear of guinea pigs by osmotic pumps. Caloric nystagmus as a marker of vestibular function and the change in auditory brainstem response (ABR) threshold as a marker of cochlear function were observed.


RESULTS
After 14 days of treatment, high gentamicin concentrations of 40 mg/mL caused canal paralysis and a rapid shift in ABR threshold. Animals exposed to low gentamicin concentrations of 4 mg/mL showed no obvious change in either vestibular or cochlear function. Animals exposed to moderate gentamicin concentrations of 12 mg/mL showed a moderate shift in ABR threshold and caloric malfunction. Histopathological examination revealed that after 14 days of treatment with 40 mg/mL gentamicin, severe cytoplasmic damage occurred in both vestibular and cochlear end organs. In animals treated with 12 mg/mL gentamicin, hair cells remained in the cochlear third turn and ampulla of the lateral semicircular canal.


CONCLUSIONS
The authors established an animal model that showed the moderate damage of inner ear with moderate-dose gentamicin. The study results indicated that the appropriate administration of gentamicin could establish a stable effect on the inner ear. It may be important to select the protocol that delivers a stable dosage of gentamicin to treat patients with Meniere's disease safely and effectively.
Okuda
Takeshi
T
Department of Otolaryngology, Yamaguchi University School of Medicine, Yamaguchi, Japan.
Sugahara
Kazuma
K
Shimogori
Hiroaki
H
Yamashita
Hiroshi
H
D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D003051:Cochlea / Q000187:drug effects* / Q000503:physiopathology*; D003593:Cytoplasm / Q000187:drug effects; D004333:Drug Administration Routes; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005839:Gentamicins / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D006168:Guinea Pigs; D009760:Nystagmus, Physiologic / Q000187:drug effects; D009995:Osmosis; D012665:Semicircular Canals / Q000187:drug effects; D014717:Vertigo / Q000139:chemically induced*; D014724:Vestibular Function Tests; D014722:Vestibule, Labyrinth / Q000187:drug effects* / Q000503:physiopathology*
D000900:Anti-Bacterial Agents; D005839:Gentamicins