{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:19:50Z","timestamp":1785766790738,"version":"3.56.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009227","name":"Iowa State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009227","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Describe the pharmacokinetics of extended-release parenteral ceftiofur (Excede<jats:sup>\u00ae<\/jats:sup>) in canine tear film and compare these concentrations to minimal inhibitory concentrations (MICs) of ceftiofur against common ocular pathogens in dogs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Six dogs of various breeds were enrolled. Disruption of blood-tear barrier was achieved with histamine-induced conjunctivitis to ensure clinical relevance of the results. Each dog received a single subcutaneous injection of 5 mg\/kg Excede<jats:sup>\u00ae<\/jats:sup>, followed by tear collection with Schirmer strips at times 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 and 240 h. Drug quantification was performed with liquid chromatography-mass spectrometry. MICs were determined for <jats:italic>Staphylococcus pseudintermedius, Streptococcus canis<\/jats:italic> and <jats:italic>Pseudomonas aeruginosa<\/jats:italic> by assessing bacterial growth (<jats:italic>n<\/jats:italic> = 10 per bacterial species) in the presence of ceftiofur at increasing concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Blood-tear barrier breakdown provided tear film concentrations of ceftiofur 3.2\u201328.9-fold higher than in the contralateral healthy eye (<jats:italic>n<\/jats:italic> = 1 dog, pilot experiment). In all six dogs, ceftiofur concentrations in tears varied from 2.3 to 637.5 ng\/mL and were detectable up to 10 days (240 h) after subcutaneous injection. However, tear levels always remained below MICs for common ocular isolates (\u2265640 ng\/mL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Ceftiofur reached the tear compartment (for up to 10 days) after a single parenteral injection, however tear concentrations were extremely variable and too low to be effective against common bacterial pathogens in dogs. Further studies with different ceftiofur dosage or other long-acting injectable antibiotics are warranted.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fvets.2022.975113","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T08:28:35Z","timestamp":1663662515000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Kinetics and minimal inhibitory concentrations of ceftiofur in tear film following extended-release parenteral administration (Excede\u00ae) in dogs"],"prefix":"10.3389","volume":"9","author":[{"given":"Anna Catherine","family":"Bowden","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Allbaugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe S.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Mochel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Sebbag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1007\/s13346-016-0339-2","article-title":"A comprehensive insight on ocular pharmacokinetics","volume":"6","author":"Agrahari","year":"2016","journal-title":"Drug Deliv Transl Res 12."},{"key":"B2","doi-asserted-by":"publisher","first-page":"457","DOI":"10.3389\/fvets.2019.00457","article-title":"Kinetics of fluorescein in tear film after eye drop instillation in beagle dogs: does size really matter?","volume":"6","author":"Sebbag","year":"2019","journal-title":"Front Vet Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"571350","DOI":"10.3389\/fvets.2020.571350","article-title":"Tear film pharmacokinetics and systemic absorption following topical administration of 1% prednisolone acetate ophthalmic suspension in dogs","volume":"7","author":"Sebbag","year":"2020","journal-title":"Front Vet Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1089\/jop.2018.0008","article-title":"Impact of flow rate, collection devices, and extraction methods on tear concentrations following oral administration of doxycycline in dogs and cats","volume":"34","author":"Sebbag","year":"2018","journal-title":"J Ocul Pharmacol Ther"},{"key":"B5","doi-asserted-by":"publisher","first-page":"508","DOI":"10.2460\/javma.249.5.508","article-title":"Tear film concentrations of doxycycline following oral administration in ophthalmologically normal dogs","volume":"249","author":"Collins","year":"2016","journal-title":"J Am Vet Med Assoc Sep."},{"key":"B6","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1111\/j.1365-2885.2007.00932.x","article-title":"Pharmacokinetics of pradofloxacin and doxycycline in serum, saliva, and tear fluid of cats after oral administration","volume":"31","author":"Hartmann","year":"2008","journal-title":"J Vet Pharmacol Ther Apr."},{"key":"B7","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1111\/vop.12479","article-title":"The presence of minocycline in the tear film of normal horses following oral administration and its anticollagenase activity","volume":"21","author":"Monk","year":"2018","journal-title":"Vet Ophthalmol Jan."},{"key":"B8","doi-asserted-by":"publisher","first-page":"833","DOI":"10.2460\/ajvr.77.8.833","article-title":"Pharmacokinetic modeling of penciclovir and BRL42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir","volume":"77","author":"Sebbag","year":"2016","journal-title":"Am J Vet Res Aug."},{"key":"B9","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1111\/vop.12764","article-title":"Utility of systemic voriconazole in equine keratomycosis based on pharmacokinetic-pharmacodynamic analysis of tear fluid following oral administration","volume":"23","author":"Tamura","year":"2020","journal-title":"Vet Ophthalmol Jul."},{"key":"B10","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1089\/jop.2019.0020","article-title":"Tear fluid pharmacokinetics following oral prednisone administration in dogs with and without conjunctivitis","volume":"35","author":"Sebbag","year":"2019","journal-title":"J Ocul Pharmacol Ther"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2566","DOI":"10.1002\/med.21716","article-title":"An eye on the dog as the scientist's best friend for translational research in ophthalmology: Focus on the ocular surface","volume":"40","author":"Sebbag","year":"2020","journal-title":"Med Res Rev Nov."},{"key":"B12","first-page":"224","article-title":"Pharmacokinetics of ceftiofur crystalline-free acid in clinically healthy dogs (Canis lupus familiaris)","volume":"55","author":"Hooper","year":"2016","journal-title":"J Am Assoc Lab Anim Sci Mar."},{"key":"B13","doi-asserted-by":"publisher","first-page":"583965","DOI":"10.3389\/fvets.2020.583965","article-title":"Prevalence and antibiotic susceptibility of bacterial isolates from dogs with ulcerative keratitis in midwestern United States","volume":"7","author":"Hewitt","year":"2020","journal-title":"Front Vet Sci."},{"key":"B14","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2021.663212","article-title":"Albumin in tears modulates bacterial susceptibility to topical antibiotics in ophthalmology","volume-title":"Front Med. (Ophthalmology)","author":"Sebbag","year":""},{"key":"B15","doi-asserted-by":"publisher","first-page":"752","DOI":"10.3389\/fphar.2019.00752","article-title":"Histamine-induced conjunctivitis and breakdown of blood-tear barrier in dogs: a model for ocular pharmacology and therapeutics","volume":"10","author":"Sebbag","year":"2019","journal-title":"Front Pharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1111\/vop.12804","article-title":"Impact of acute conjunctivitis on ocular surface homeostasis in dogs","volume":"23","author":"Sebbag","year":"2020","journal-title":"Vet Ophthalmol Sep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.aca.2004.02.017","article-title":"High-performance liquid chromatographic-UV detection analysis of ceftiofur and its active metabolite desfuroylceftiofur in horse plasma and synovial fluid after regional intravenous perfusion and systemic intravenous injection of ceftiofur sodium","volume":"512","author":"De Baere","year":"2004","journal-title":"Analytica Chimica Acta"},{"key":"B18","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1111\/vop.12502","article-title":"Tear fluid collection in dogs and cats using ophthalmic sponges","volume":"21","author":"Sebbag","year":"2018","journal-title":"Vet Ophthalmol May."},{"key":"B19","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1111\/vop.12876","article-title":"Influence of Schirmer strip wetness on volume absorbed, volume recovered, and total protein content in canine tears","volume":"24","author":"Bertram","year":"2021","journal-title":"Vet Ophthalmol Jul."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.vetmic.2009.12.013","article-title":"Assessing the antimicrobial susceptibility of bacteria obtained from animals","volume":"141","author":"Schwarz","year":"2010","journal-title":"Vet Microbiol Feb."},{"key":"B21","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/S0034-5288(18)31742-9","article-title":"Plasma and tear concentrations of antibiotics administered parenterally to cattle","volume":"39","author":"Punch","year":"1985","journal-title":"Res Vet Sci Sep."},{"key":"B22","doi-asserted-by":"publisher","first-page":"571457","DOI":"10.3389\/fvets.2020.571457","article-title":"Pharmacokinetics of oral prednisone at various doses in dogs: preliminary findings using a na\u00efve pooled-data approach","volume":"7","author":"Sebbag","year":"2020","journal-title":"Front Vet Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.2460\/ajvr.2004.65.1185","article-title":"Efficacy of a long-acting formulation of ceftiofur crystalline-free acid for the treatment of naturally occurring infectious bovine keratoconjunctivitis","volume":"65","author":"Dueger","year":"2004","journal-title":"Am J Vet Res Sep."},{"key":"B24","first-page":"E1","article-title":"In vitro comparison of Staphylococcus pseudintermedius susceptibility to common cephalosporins used in dogs","volume":"11","author":"Westermeyer","year":"2010","journal-title":"Vet Ther."},{"key":"B25","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.vetmic.2008.02.018","article-title":"Antimicrobial resistance and genetic characterization of fluoroquinolone resistance of Pseudomonas aeruginosa isolated from canine infections","volume":"131","author":"Rubin","year":"2008","journal-title":"Vet Microbiol Sep 18."},{"key":"B26","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1093\/jac\/dkm269","article-title":"Occurrence of antimicrobial resistance in bacteria from diagnostic samples from dogs","volume":"60","author":"Pedersen","year":"2007","journal-title":"J Antimicrob Chemother Oct."},{"key":"B27","doi-asserted-by":"publisher","first-page":"580396","DOI":"10.3389\/fvets.2021.580396","article-title":"Case report: clinical remission in a cat with severe bilateral eosinophilic keratitis receiving combined immunosuppressive therapy (triamcinolone acetonide and tacrolimus)","volume":"8","author":"Romaneck","year":"2021","journal-title":"Front Vet Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1053\/j.tcam.2015.07.006","article-title":"Corneal emergencies","volume":"30","author":"Belknap","year":"2015","journal-title":"Top Companion Anim Med Sep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1111\/jvp.12469","article-title":"Pharmacokinetic profile of Ceftiofur Hydrochloride Injection in lactating Holstein dairy cows","volume":"41","author":"Wang","year":"2018","journal-title":"J Vet Pharmacol Ther Apr."},{"key":"B30","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1111\/vop.12840","article-title":"Impact of diurnal variation, sex, tear collection method, and disease state on tear protein levels in dogs","volume":"23","author":"Page","year":"2020","journal-title":"Vet Ophthalmol Nov."},{"key":"B31","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1111\/vop.12822","article-title":"Serum albumin and total protein concentration in the tear film of horses with healthy or diseased eyes","volume":"24","author":"Terhaar","year":"2021","journal-title":"Vet Ophthalmol Jan."},{"key":"B32","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1089\/jop.2019.0038","article-title":"Fluorophotometric assessment of tear volume and turnover rate in healthy dogs and cats","volume":"35","author":"Sebbag","year":"2019","journal-title":"J Ocul Pharmacol Ther Nov."},{"key":"B33","doi-asserted-by":"crossref","DOI":"10.1111\/vop.13008","article-title":"Evaluation of conjunctival graft procedures and factors that lead to graft complications in canine cases","volume-title":"Vet Ophthalmol","author":"Osinchuk","year":"2022"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2022.975113\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T09:57:01Z","timestamp":1663840621000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2022.975113\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,20]]},"references-count":33,"alternative-id":["10.3389\/fvets.2022.975113"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2022.975113","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,20]]},"article-number":"975113"}}