Ototoxicity caused by once- and twice-daily administration of amikacin in rabbits

Abstract

Objective: The cochleotoxic effects of aminoglycosides, such as amikacin, are well-established. The aim of the present study was to investigate the possible differences in cochleotoxic effects between once-daily administration (ODA) and twice-daily administration (TDA) of amikacin simulating pediatric dosing. Methods: Twenty-one rabbits were used. Seven animals received intramuscularly amikacin once daily (ODA-group) and seven received the drug twice daily (TDA-group), for a total time period of 2 weeks. All the animals were subjected to Distortion Product Otoacoustic Emissions (DPOAEs) every 3 days since beginning of the experiment. The rest 7 animals did not receive any medication and served as controls (Control group). Two measurements (7 and 14 days) were obtained following the cease of drug administration. Results: Reduced cochlear activity (as depicted in the respective reduced DPOAE-amplitudes) compared to the pre-treatment state was found in both ODA- and TDA-groups. Cochlear activity was reduced at a wider range of frequencies (from 593 to 4031 Hz in TDA-group and from 593 to 1093 Hz in ODA-group) and to a higher degree in group B than in group A. Cochlear activity was reduced earlier in ODA-group than in TDA-group. No differences to the pre-treatment state were observed in the control group. Conclusions: The above findings suggest that less frequent administration in higher dose of amikacin is associated with minimal cochleotoxicity. (C) 2010 Elsevier Ireland Ltd. All rights reserved.