Ototoxicity associated with topical administration of diclofenac sodium as an otic drop: An experimental animal study Engin Acioglu, MD a, 1 , Ozgur Yigit, MD a , Firat Onur, MD a, * , Ahmet Atas, PhD b , Ela Araz Server, MD a , Eyup Kara, MSc b a Department of Otorhinolaryngology & Head and Neck Surgery, University of Health Sciences, Istanbul Training and Research Hospital, Fatih, Istanbul, Turkey b Department of Audiology, Istanbul University Faculty of Health Sciences, Fatih, Istanbul, Turkey article info Article history: Received 7 February 2017 Received in revised form 17 April 2017 Accepted 24 April 2017 Available online 27 April 2017 Keywords: Ototoxicity Diclofenac sodium Anti-inflammatory ABR abstract Objectives: The aim of the study is to evaluate the ototoxicity of topical diclofenac sodium in comparison to positive and negative controls prior to the investigation of analgesic and anti-inflammatory efficacy of the agent in otic administration. Methods: Twenty four ears of 12 guinea pigs were included in the study. Wide myringotomy was per- formed on all tympanic membranes under general anesthesia and auditory brainstem responses (ABR) were evaluated. The subjects were separated into four groups, two groups received diclofenac sodium at low and high doses, positive controls received gentamicin and negative controls received isotonic sodium chloride topically for 14 days and ABRs were reevaluated. Results: No significant difference were observed between the pre and post-treatment click response, 1 kHz and 8 kHz response threshold levels after isotonic sodium chloride administration. All threshold levels were elevated in the positive control group. In the low and high dose diclofenac sodium groups, click response, 1 kHz and 8 kHz response threshold levels were significantly higher compared to the baseline values. Pre and post-treatment mean threshold level changes were not significantly different between the low and high dose diclofenac sodium groups. Pre and post-treatment mean threshold level changes in the gentamicin group were not significantly different from low or high dose diclofenac so- dium groups. Conclusion: Diclofenac sodium, considered as an analgesic and anti-inflammatory otic preparation, is shown to be as ototoxic as gentamicin in chronic use which may lead to loss of hearing especially when used topically in chronic otitis cases with tympanic membrane damage. © 2017 Elsevier B.V. All rights reserved. 1. Introduction Topical treatments are commonly used in outer, middle and even some of the inner ear diseases. Low likelihood of systemic side effects and achieving higher concentrations at the target site when compared to systemic administration favors the development and use of topical agents [1]. Topical antibacterial or antifungal preparations are frequently used together with a topical corticosteroid as an anti-inflammatory agent for the treatment of inflammatory disorders like otitis externa or chronic purulent otorrhea. Non-steroid anti-inflammatory drugs (NSAIDs) have analgesic and antipyretic properties as well as anti-inflammatory effects resembling corticosteroids [2]. NSAIDs which may provide both anti-inflammatory and analgesic effects are commonly used as topical agents in literally all disorders of dermal and mucosal sur- faces [3]. For instance, in ophthalmology, topical NSAIDs are commonly used following incisional laser surgery, corneal erosions or abrasions to enhance patient comfort. However, topical NSAIDs are currently not available in the otological practice of ENT [4]. The main reason may be local ototoxic effect of some NSAIDs. Despite a favorable safe profile with rare systemic side effects, topical * Corresponding author. Present Affiliation: Department of Otolaryngology Head and Neck Surgery, Babaeski State Hospital, Babaeski, Kırklareli, Turkey. E-mail addresses: drengin@hotmail.com (E. Acioglu), dryigit@yahoo.com (O. Yigit), firat.onr@hotmail.com (F. Onur), atasahmet1@gmail.com (A. Atas), serverela@hotmail.com (E.A. Server), karaeyup@yahoo.com (E. Kara). 1 Present Affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Memorial Atas ¸ ehir Hospital, Atas ¸ ehir, Istanbul, Turkey. Contents lists available at ScienceDirect International Journal of Pediatric Otorhinolaryngology journal homepage: http://www.ijporlonline.com/ http://dx.doi.org/10.1016/j.ijporl.2017.04.039 0165-5876/© 2017 Elsevier B.V. All rights reserved. International Journal of Pediatric Otorhinolaryngology 98 (2017) 110e115