Topical gentamicin and ethacrynic acid: effects on cochlear function.
OBJECTIVE
To determine whether concurrent intravenous administration of the loop diuretic ethacrynic acid potentiates the toxicity of the aminoglycoside antibiotic gentamicin applied topically on the round window.


METHODS
The authors studied the effects on cochlear sensitivity of co-administered intracardiac ethacrynic acid (40 mg/kg) and high-dose topical gentamicin solution (100%) applied to the round window. Comparisons were made with animals receiving ethacrynic acid plus systemic gentamicin (100 mg/kg); topical gentamicin alone; systemic gentamicin alone; and intravenous ethacrynic acid alone.


METHODS
Experiments were carried out on pigmented guinea pigs weighing 400 to 500 g. Changes in cochlear function were characterized by monitoring shifts in compound action potential (CAP) thresholds by use of chronic indwelling electrodes implanted at the round window, vertex, and contralateral mastoid.


RESULTS
After 20 days animals receiving ethacrynic acid in combination with topical gentamicin to the round window failed to demonstrate a significant deterioration in cochlear sensitivity, whereas all animals receiving systemic gentamicin plus ethacrynic acid experienced profound increases in CAP thresholds.


CONCLUSIONS
This study supports the contention that ethacrynic acid potentiates aminoglycoside ototoxicity by facilitating the entry of the antibiotics from the systemic circulation into the endolymph. In addition, this study answers important clinical concerns regarding the safety of the use of topical aminoglycoside agents in combination with loop diuretics.
Hearing Research Laboratories, Division of Otolaryngology--Head and Neck Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
B J
BJ
Conlon
S D
SD
McSwain
D W
DW
Smith
D000200:Action Potentials / Q000187:drug effects; D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001309:Auditory Threshold / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology*; D004232:Diuretics / Q000009:adverse effects*; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004567:Electrodes, Implanted; D004976:Ethacrynic Acid / Q000009:adverse effects*; D005839:Gentamicins / Q000009:adverse effects*; D006168:Guinea Pigs; D007262:Infusions, Intravenous; D011897:Random Allocation
D000900:Anti-Bacterial Agents; D004232:Diuretics; D005839:Gentamicins; D004976:Ethacrynic Acid