{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T17:16:23Z","timestamp":1775582183064,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T00:00:00Z","timestamp":1422921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:sec><jats:title>Objectives\/Hypothesis<\/jats:title><jats:p>Two undesired effects of the aminoglycoside antibiotic gentamicin are ototoxicity and nephrotoxicity. This study investigated if these adverse effects vary according to the circadian time of its administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>This study entails laboratory animal research.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four groups of Sprague\u2010Dawley rats were synchronized to a 12:12 light\/dark schedule. Each group receiving the antibiotic (100 mg\/kg gentamicin sulfate) at a different circadian time. Auditory brainstem response was obtained at pretreatment and at 2, 4, and 6 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At all measured frequencies, hearing losses were significantly (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001) greater when gentamicin was administered during the diurnal rest span than the nighttime activity span. At 4 weeks, the average total hearing loss, quantified by elevation of threshold values over the tested auditory frequencies, was 31.3 and 25.6 dB for the 2 hours after lights on (HALO) and 8 HALO groups, respectively. The loss progressed at 6 weeks to 42.5 (2 HALO) and 37.5 (8 HALO) dB. At 6 weeks, the 14 and 20 HALO groups had losses of 17.5 and 26.3 dB, respectively. Trough serum gentamicin concentration significantly (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.01) increased during treatment, being the highest at 4 weeks. Urine urea nitrogen 24\u2010hour levels of the 2 and 8 HALO groups differed significantly (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.01) from the 14 and 20 HALO groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Ototoxicity was greater when gentamicin was administered during their diurnal rest than during nocturnal activity. A dosing paradigm may be used to deliver a lower therapeutic antimicrobial concentration during the nighttime rest period when the studied adverse effects are of highest risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA <jats:italic>Laryngoscope<\/jats:italic>, 125:E252\u2013E256, 2015<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.25116","type":"journal-article","created":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T14:30:03Z","timestamp":1422973803000},"source":"Crossref","is-referenced-by-count":15,"title":["Circadian variation of gentamicin toxicity in rats"],"prefix":"10.1002","volume":"125","author":[{"given":"William","family":"McKinney","sequence":"first","affiliation":[{"name":"School of Public Health  University of Texas Health Science Center Houston Texas U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Al","family":"Yonovitz","sequence":"additional","affiliation":[{"name":"Department of Communicative Sciences and Disorders  University of Montana Missoula Montana U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael H.","family":"Smolensky","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering  University of Texas at Austin Austin Texas U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,2,3]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"1167","volume-title":"The Pharmacological Basis of Therapeutics","author":"Weinstein L","year":"1975"},{"key":"e_1_2_7_3_1","volume-title":"Trends in Chronobiology","author":"Hekkens W","year":"1988"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198207050-00002"},{"issue":"1","key":"e_1_2_7_5_1","first-page":"95","article-title":"Clinical chronopharmacokinetics [in French]","volume":"15","author":"Reinberg A","year":"1984","journal-title":"J 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