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Comparative ototoxicity of chloramphenicol and kanamycin with ethacrynic acid
Abstract:
Chloramphenicol is not ototoxic if administered for systemic effect, but topical applications of it to the middle ear produce severe cochlear toxic effects. Ethacrynic acid potentiates the ototoxicity of aminoglycosides. Guinea pigs were administered chloramphenicol or kanamycin sulfate with ethacrynic acid to compare the ototoxicity of chloramphenicol and ethacrynic acid with the ototoxicity of kanamycin and ethacrynic acid. Preyer's reflex audiometry and measurement of the endocochlear dc potential, the cochlear microphonics, and the negative potential of the organ of Corti indicate that ethacrynic acid does not potentiate the ototoxicity of chloramphenicol. There is not even indirect evidence that the blood-cochlear barrier for chloramphenicol is altered by ethacrynic acid. Assuming that the ototoxicity of chloramphenicol and ethacrynic acid are similar for man and guinea pig, the combination of the administration of chloramphenicol and ethacrynic acid of systemic effect in dosages commonly used clinically should not produce greater ototoxicity than either agent administered alone.
Insights
Ethacrynic acid does not worsen chloramphenicol ototoxicity. Combining these drugs systemically is likely safe, as ethacrynic acid only potentiates aminoglycoside ototoxicity, not chloramphenicol cochlear effects.
Area of Science:
- Ototoxicology
- Pharmacology
- Neuroscience
Background:
- Systemic chloramphenicol is generally not ototoxic, but topical application to the middle ear causes cochlear toxicity.
- Ethacrynic acid is known to potentiate the ototoxicity of aminoglycoside antibiotics.
Purpose of the Study:
- To investigate whether ethacrynic acid potentiates the ototoxicity of chloramphenicol.
- To compare the ototoxicity of chloramphenicol plus ethacrynic acid with kanamycin sulfate plus ethacrynic acid.
Main Methods:
- Guinea pigs were administered chloramphenicol or kanamycin sulfate concurrently with ethacrynic acid.
- Ototoxicity was assessed using Preyer's reflex audiometry, endocochlear dc potential, cochlear microphonics, and organ of Corti negative potential measurements.
Main Results:
- Ethacrynic acid did not potentiate the ototoxicity of chloramphenicol.
- No evidence suggested that ethacrynic acid alters the blood-cochlear barrier for chloramphenicol.
- Kanamycin sulfate plus ethacrynic acid served as a positive control for potentiated ototoxicity.
Conclusions:
- Systemic administration of chloramphenicol with ethacrynic acid is unlikely to cause greater ototoxicity than either agent alone.
- Findings suggest a differential effect of ethacrynic acid on the ototoxicity of different drug classes.