{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T17:51:54Z","timestamp":1760982714547},"reference-count":37,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2009,1,2]],"date-time":"2009-01-02T00:00:00Z","timestamp":1230854400000},"content-version":"vor","delay-in-days":93,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Objectives\/Hypothesis:<\/jats:bold> To establish safe dosing protocols for the treatment of patients with Meniere's disease with intratympanic gentamicin.<\/jats:p><jats:p><jats:bold>Study Design:<\/jats:bold> A validated computer model of gentamicin dispersion in the inner ear fluids was used to calculate cochlear drug levels resulting from specific clinical delivery protocols. Dosing in the cochlea was compared with changes of hearing sensitivity for 568 patients reported in 19 publications.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Cochlear drug levels were calculated based on the concentration and volume of gentamicin applied, the time the drug remained in the middle ear, and on the specific timing of injections. Time courses were quantified in terms of the maximum concentration (<jats:italic>C<\/jats:italic>\n<jats:sub>max<\/jats:sub>) and the area under the curve of the drug at specific cochlear locations.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Drug levels resulting from single, \u201cone\u2010shot\u201d injections were typically lower than those from repeated or continuous application protocols. Comparison of hearing sensitivity changes with gentamicin dosing revealed a flat curve with a near\u2010zero mean for lower doses, suggesting that hearing changes with doses over this range were probably unrelated to the applied drug. Higher intracochlear doses were generated with repeated or continuous delivery protocols, which in some cases caused substantial hearing losses and an increased incidence of deafened ears.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> One\u2010shot application protocols produce gentamicin doses in the cochlea that have minimal risk to hearing at the frequencies tested. Repeated or continuous application protocols result in higher doses that in some cases damage hearing. The high variability of hearing changes, even with low gentamicin doses, calls into question the rationale for using individual hearing changes to titrate the applied dose.<\/jats:p>","DOI":"10.1097\/mlg.0b013e31817d01cd","type":"journal-article","created":{"date-parts":[[2008,9,24]],"date-time":"2008-09-24T07:08:41Z","timestamp":1222240121000},"page":"1793-1800","source":"Crossref","is-referenced-by-count":46,"title":["Dependence of Hearing Changes on the Dose of Intratympanically Applied Gentamicin: A Meta\u2010Analysis Using Mathematical Simulations of Clinical Drug Delivery Protocols"],"prefix":"10.1002","volume":"118","author":[{"given":"Alec N.","family":"Salt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth M.","family":"Gill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan K.","family":"Plontke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,2]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"409","article-title":"The intratympanic treatment of Meniere's disease with ototoxic antibiotics. A follow\u2010up study of 55 cases","volume":"56","author":"Lange G","year":"1977","journal-title":"Laryngol Rhinol Otol"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00463571"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-997832"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(01)00223-4"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-006-0034-y"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00129492-200211000-00026"},{"key":"e_1_2_6_8_2","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/S0030-6665(20)30156-0","article-title":"Use of sustained release vehicles in the treatment of Meniere's disease","volume":"30","author":"Hoffer ME","year":"1997","journal-title":"Otolaryngol Clin North Am"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0194-5998(98)70097-X"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1053\/hn.1999.v120.a91762"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/MLG.0b013e318058a06b"},{"key":"e_1_2_6_12_2","first-page":"278","article-title":"Intratympanic gentamicin instillation as treatment of unilateral Meniere's disease: update of an ongoing study","volume":"3","author":"Nedzelski JM","year":"1993","journal-title":"Am J Otol"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-199701000-00017"},{"key":"e_1_2_6_14_2","first-page":"44","article-title":"Intratympanic gentamicin therapy for Meniere's disease","volume":"18","author":"Hirsch BE","year":"1997","journal-title":"Am J Otol"},{"key":"e_1_2_6_15_2","first-page":"52","article-title":"Intratympanic gentamicin in Meniere's disease: results of therapy","volume":"18","author":"Murofushi T","year":"1997","journal-title":"Am J Otol"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-199701000-00012"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1177\/019459989811800505"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2273.1998.00092.x"},{"key":"e_1_2_6_19_2","first-page":"435","article-title":"Intratympanic gentamicin injection for the treatment of Meniere's disease","volume":"19","author":"Youssef TF","year":"1998","journal-title":"Am J Otol"},{"key":"e_1_2_6_20_2","first-page":"209","article-title":"Intratympanic gentamicin for control of vertigo in Meniere's disease: vestibular signs that specify completion of therapy","volume":"20","author":"Minor LB","year":"1999","journal-title":"Am J Otol"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb08658.x"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1053\/hn.1999.v120.a91763"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200008000-00014"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1080\/000164801300102879"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1067\/mhn.2001.112310"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/00129492-200207000-00018"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200305000-00009"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1258\/0022215041615083"},{"key":"e_1_2_6_29_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3233\/VES-2006-161-207","article-title":"Recovery of subjective visual horizontal after unilateral vestibular deafferentation by intratympanic instillation of gentamicin","volume":"16","author":"Takai Y","year":"2006","journal-title":"J Vestib Res"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1080\/00016480600951475"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-199910000-00021"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.3109\/00016488809107371"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(88)90111-6"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1097\/MAO.0b013e318161aaae"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112463"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1121\/1.399052"},{"key":"e_1_2_6_37_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0194-5998(95)70102-8","volume":"113","author":"Committee on hearing and equilibrium guidelines for the diagnosis and evaluation of therapy in Meni\u00e8re's disease. American Academy of Otolaryngology\u2010Head Neck Foundation, Inc.","year":"1995","journal-title":"Otolaryngol Head Neck Surg"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1097\/00129492-200407000-00023"}],"container-title":["The Laryngoscope"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1097%2FMLG.0b013e31817d01cd","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1097\/MLG.0b013e31817d01cd","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T13:38:17Z","timestamp":1694957897000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1097\/MLG.0b013e31817d01cd"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10]]},"references-count":37,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2008,10]]}},"alternative-id":["10.1097\/MLG.0b013e31817d01cd"],"URL":"https:\/\/doi.org\/10.1097\/mlg.0b013e31817d01cd","archive":["Portico"],"relation":{},"ISSN":["0023-852X","1531-4995"],"issn-type":[{"value":"0023-852X","type":"print"},{"value":"1531-4995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10]]}}}