International Journal of Pediatric Otorhinolaryngology
Volume 74, Issue 4 , Pages 361-364, April 2010

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

  • Pavlos Pavlidis

      Affiliations

    • 2nd Department of Otolaryngology, School of Medicine, Aristotle University, Papageorgiou G.H., Thessaloniki, Greece
    • 2nd Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Greece
    • Department of Otolaryngology, School of Medicine, University of Thessaly, Larissa, Greece
  • ,
  • Vasilios Nikolaidis

      Affiliations

    • 2nd Department of Otolaryngology, School of Medicine, Aristotle University, Papageorgiou G.H., Thessaloniki, Greece
  • ,
  • Haralampos Gouveris

      Affiliations

    • Department of Otolaryngology, School of Medicine, University of Thessaly, Larissa, Greece
  • ,
  • Elias Papadopoulos

      Affiliations

    • Veterinary School, Aristotle University of Thessaloniki, Greece
  • ,
  • Georgios Kekes

      Affiliations

    • 2nd Department of Otolaryngology, School of Medicine, Aristotle University, Papageorgiou G.H., Thessaloniki, Greece
  • ,
  • Dimitrios Kouvelas

      Affiliations

    • 2nd Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Greece
    • Corresponding Author InformationCorresponding author at: P.O. Box 1532, 54006 Thessaloniki, Greece. Tel.: +30 2310 999335; fax: +30 2310 999335.

Received 6 July 2009; received in revised form 21 December 2009; accepted 22 December 2009.

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 4031Hz in TDA-group and from 593 to 1093Hz 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.

Keywords: Ototoxicity, Cochlear, Amikacin, Post-antibiotic effect, Distortion Product Otoacoustic Emissions

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PII: S0165-5876(10)00002-9

doi:10.1016/j.ijporl.2009.12.018

International Journal of Pediatric Otorhinolaryngology
Volume 74, Issue 4 , Pages 361-364, April 2010