Relation of dosing regimen to aminoglycoside ototoxicity: evaluation of auditory damage in the guinea pig.
Groups of guinea pigs were injected intramuscularly for 21 days with netilmicin or amikacin 150 mg/kg/day by one or three daily injections. Amikacin was also tested at 225 mg/kg/day with each dosing regimen. Auditory function was evaluated during the experiment by reflexological and electrophysiological tests. Morphological damage to the inner ear was also evaluated. Netilmicin had no effect on the auditory function nor did it damage the organ of Corti. Conversely, amikacin impaired the auditory function and produced loss of hair cells in a dose-related manner. The effect was equally marked with both dosing regimens of 225 mg/kg/day, whereas a slight decrease of auditory impairment was observed with 150 mg/kg administered once a day. The data suggest that administration of a single daily dose of aminoglycosides does not increase the risk of ototoxicity specifically associated with each compound.
Bamonte
F
F
Research Laboratories, Schering-Plough S.p.A., Comazzo, Milan, Italy.
Dionisotti
S
S
Gamba
M
M
Ongini
E
E
Arpini
A
A
Melone
G
G
D000583:Amikacin / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001307:Auditory Perception / Q000187:drug effects; D003051:Cochlea / Q000648:ultrastructure; D004334:Drug Administration Schedule; D007758:Ear, Inner / Q000187:drug effects*; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000648:ultrastructure*; D008297:Male; D008855:Microscopy, Electron, Scanning; D009428:Netilmicin / Q000008:administration & dosage / Q000494:pharmacology*; D009925:Organ of Corti / Q000187:drug effects / Q000648:ultrastructure; D013997:Time Factors
D009428:Netilmicin; D000583:Amikacin