{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:45:28Z","timestamp":1743554728895,"version":"3.38.0"},"reference-count":31,"publisher":"American Veterinary Medical Association (AVMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>OBJECTIVE<\/jats:bold> To determine the pharmacokinetics of florfenicol, terbinafine, and betamethasone acetate after topical application to canine auricular skin and the influence of synthetic canine cerumen on pharmacokinetics.<\/jats:p>\n<jats:p><jats:bold>SAMPLE<\/jats:bold> Auricular skin from 6 euthanized shelter dogs (3 females and 3 neutered males with no visible signs of otitis externa).<\/jats:p>\n<jats:p><jats:bold>PROCEDURES<\/jats:bold> Skin adjacent to the external opening of the ear canal was collected and prepared for use in a 2-compartment flow-through diffusion cell system to evaluate penetration of an otic gel containing florfenicol, terbinafine, and betamethasone acetate over a 24-hour period. Radiolabeled <jats:sup>14<\/jats:sup>C-terbinafine hydrochloride and <jats:sup>3<\/jats:sup>H-betamethasone acetate were added to the gel to determine dermal penetration and distribution. Florfenicol absorption was determined by use of high-performance liquid chromatography\u2013UV detection. Additionally, the effect of synthetic canine cerumen on the pharmacokinetics of all compounds was evaluated.<\/jats:p>\n<jats:p><jats:bold>RESULTS<\/jats:bold> During the 24-hour experiment, mean \u00b1 SD percentage absorption without the presence of synthetic canine cerumen was 0.28 \u00b1 0.09% for 3H-betamethasone acetate, 0.06 \u00b1 0.06% for florfenicol, and 0.06 \u00b1 0.02% for 14C-terbinafine hydrochloride. Absorption profiles revealed no impact of synthetic canine cerumen on skin absorption for all 3 active compounds in the gel or on skin distribution of <jats:sup>3<\/jats:sup>H-betamethasone acetate and <jats:sup>14<\/jats:sup>C-terbinafine hydrochloride.<\/jats:p>\n<jats:p><jats:bold>CONCLUSIONS AND CLINICAL RELEVANCE<\/jats:bold> <jats:sup>3<\/jats:sup>H-betamethasone acetate, <jats:sup>14<\/jats:sup>C-terbinafine hydrochloride, and florfenicol were all absorbed in vitro through healthy auricular skin specimens within the first 24 hours after topical application. Synthetic canine cerumen had no impact on dermal absorption in vitro, but it may serve as a temporary reservoir that prolongs the release of topical drugs.<\/jats:p>","DOI":"10.2460\/ajvr.79.3.333","type":"journal-article","created":{"date-parts":[[2018,2,21]],"date-time":"2018-02-21T17:13:34Z","timestamp":1519233214000},"page":"333-341","source":"Crossref","is-referenced-by-count":1,"title":["Impact of synthetic canine cerumen on in vitro penetration of auricular skin of dogs by florfenicol, terbinafine, and betamethasone acetate"],"prefix":"10.2460","volume":"79","author":[{"given":"Sarah","family":"Ehling","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald E.","family":"Baynes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"B\u00e4umer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"Vet Rec","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1136\/vr.158.16.533","article-title":"Survey of the prevalence, diagnosis and treatment of dermatological conditions in small animals in general practice","volume":"158","author":"PB","year":"2006"},{"key":"ref2","series-title":"Vet Dermatol","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1111\/j.1365-3164.2007.00619.x","article-title":"Aetiology of canine otitis externa: a retrospective study of 100 cases","volume":"18","author":"MN","year":"2007"},{"key":"ref3","series-title":"Vet Clin North Am Small Anim Pract","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.cvsm.2003.10.006","article-title":"Causes of otitis externa","volume":"34","author":"Rosser","year":"2004"},{"key":"ref4","series-title":"Indian J Otolaryngol Head Neck Surg","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s12070-009-0063-z","article-title":"A comparative study of ceruminolytic agents","volume":"61","author":"P","year":"2009"},{"key":"ref5","series-title":"Pathologic basis of veterinary disease expert consult","article-title":"Pathology of organ systems","author":"JF","year":"2012"},{"year":"2017","series-title":"OSURNIA otic gel for dogs","key":"ref6"},{"key":"ref7","series-title":"J Vet Sci","doi-asserted-by":"publisher","first-page":"163","DOI":"10.4142\/jvs.2012.13.2.163","article-title":"Histologic morphology and involucrin, filaggrin, and keratin expression in normal canine skin from dogs of different breeds and coat types","volume":"13","author":"S","year":"2012"},{"key":"ref8","series-title":"J Pharm Sci","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1002\/jps.2600760608","article-title":"In vivo percutaneous penetration of some organic compounds related to anatomic site in humans: predictive assessment by the stripping method","volume":"76","author":"A","year":"1987"},{"key":"ref9","series-title":"J Invest Dermatol","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1111\/1523-1747.ep12505567","article-title":"Interspecies and interregional analysis of the comparative histologic thickness and laser Doppler blood flow measurements at five cutaneous sites in nine species","volume":"95","author":"Monteiro-Riviere","year":"1990"},{"key":"ref10","series-title":"Adv Drug Deliv Rev","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/S0169-409X(01)00158-2","article-title":"Veterinary drug delivery: potential for skin penetration enhancement","volume":"50","author":"BM","year":"2001"},{"key":"ref11","series-title":"J Vet Pharmacol Ther","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1111\/j.1365-2885.2010.01246.x","article-title":"The correlation between epidermal lipid composition and morphologic skin characteristics with percutaneous permeation: an interspecies comparison of substances with different lipophilicity","volume":"34","author":"J","year":"2011"},{"year":"2017","series-title":"Guidance notes on dermal absorption. Series on testing and assessment: No. 156","key":"ref12"},{"series-title":"OECD guideline for the testing of chemicals. Skin absorption: in vitro method","key":"ref13"},{"key":"ref14","series-title":"Vet Dermatol","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1111\/j.1365-3164.2009.00853.x","article-title":"Histological changes in the external ear canal of dogs with otitis externa","volume":"20","author":"HP","year":"2009"},{"key":"ref15","series-title":"Food Chem Toxicol","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1016\/j.fct.2006.05.020","article-title":"Skin decontamination: importance of the wash-in effect","volume":"44","author":"RP","year":"2006"},{"key":"ref16","series-title":"J Pharm Sci","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1002\/jps.2600740117","article-title":"Methods for in vitro percutaneous absorption studies IV: the flow-through diffusion cell","volume":"74","author":"RL","year":"1985"},{"key":"ref17","series-title":"BMC Vet Res","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/1746-6148-9-70","article-title":"Ceruminal diffusion activities and ceruminolytic characteristics of otic preparations\u2014an in-vitro study","volume":"9","author":"J","year":"2013"},{"key":"ref18","series-title":"Vet Dermatol","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1111\/j.1365-3164.2010.00938.x","article-title":"Stratum corneum removal facilitates experimental sensitization to mite allergens in atopic dogs","volume":"22","author":"T","year":"2011"},{"key":"ref19","series-title":"Adv Drug Deliv Rev","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.addr.2012.06.010","article-title":"Finite and infinite dosing: difficulties in measurements, evaluations and predictions","volume":"65","author":"D","year":"2013"},{"key":"ref20","series-title":"Acta Biomater","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.actbio.2015.03.024","article-title":"Covalently-crosslinked mucin biopolymer hydrogels for sustained drug delivery","volume":"20","author":"CV","year":"2015"},{"key":"ref21","series-title":"Polymer (Guildf)","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1016\/j.polymer.2008.01.027","article-title":"Hydrogels in drug delivery: progress and challenges","volume":"49","author":"TR","year":"2008"},{"key":"ref22","series-title":"Skin Pharmacol Physiol","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1159\/000074057","article-title":"Factors affecting the formation of a skin reservoir for topically applied solutes","volume":"17","author":"MS","year":"2004"},{"key":"ref23","series-title":"Br J Anaesth Contin Educ Anaesth","first-page":"171","article-title":"Transdermal drug delivery: principles and opioid therapy","volume":"7","author":"L","year":"2007"},{"key":"ref24","series-title":"Res Vet Sci","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.rvsc.2007.04.001","article-title":"Pharmacokinetics of florfenicol and its metabolite, florfenicol amine, in dogs","volume":"84","author":"BK","year":"2008"},{"key":"ref25","series-title":"Skin Pharmacol Physiol","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1159\/000288163","article-title":"Enhanced absorption through damaged skin: an overview of the in vitro human model","volume":"23","author":"S","year":"2010"},{"key":"ref26","series-title":"J Dermatol Sci","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/0923-1811(93)90076-2","article-title":"Skin barrier defect in atopic dermatitis: increased permeability of the stratum corneum using dimethyl sulfoxide and theophylline","volume":"5","author":"T","year":"1993"},{"key":"ref27","series-title":"Eur J Pharm Sci","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/S0928-0987(01)00167-1","article-title":"Novel mechanisms and devices to enable successful transdermal drug delivery","volume":"14","author":"BW","year":"2001"},{"key":"ref28","series-title":"Vet Dermatol","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1111\/vde.12382","article-title":"Prior antimicrobial use as a risk factor for resistance in selected Staphylococcus pseudintermedius isolates from the skin and ears of dogs","volume":"27","author":"G","year":"2016"},{"key":"ref29","series-title":"Berl Munch Tierarztl Wochenschr","first-page":"441","article-title":"Antibiotic plasma levels in dogs with otitis externa treated routinely with various topical preparations","volume":"125","author":"M","year":"2012"},{"key":"ref30","series-title":"Results Pharma Sci","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.rinphs.2014.09.002","article-title":"Development and validation of an alternative disturbed skin model by mechanical abrasion to study drug penetration","volume":"4","author":"P","year":"2014"},{"key":"ref31","series-title":"Toxicol In Vitro","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.tiv.2016.10.004","article-title":"Further development of an in vitro model for studying the penetration of chemicals through compromised skin","volume":"38","author":"DJ","year":"2017"}],"container-title":["American Journal of Veterinary Research"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/79\/3\/ajvr.79.3.333.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/79\/3\/ajvr.79.3.333.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/79\/3\/ajvr.79.3.333.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T12:42:32Z","timestamp":1741351352000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/79\/3\/ajvr.79.3.333.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3]]},"references-count":31,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.2460\/ajvr.79.3.333","relation":{},"ISSN":["0002-9645"],"issn-type":[{"type":"print","value":"0002-9645"}],"subject":[],"published":{"date-parts":[[2018,3]]}}}