{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:44:20Z","timestamp":1792205060330,"version":"4.4.0"},"reference-count":38,"publisher":"American Veterinary Medical Association (AVMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["javma"],"published-print":{"date-parts":[[2013,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>Objective<\/jats:bold>\u2014To assess tear and plasma concentrations of doxycycline following oral administration to northern elephant seals (<jats:italic>Mirounga angustirostris<\/jats:italic>).<\/jats:p>\n<jats:p><jats:bold>Design<\/jats:bold>\u2014Pharmacokinetic study.<\/jats:p>\n<jats:p><jats:bold>Animals<\/jats:bold>\u201418 juvenile northern elephant seals without signs of ocular disease.<\/jats:p>\n<jats:p><jats:bold>Procedures<\/jats:bold>\u2014Study seals were receiving no medications other than a multivitamin and were free from signs of ocular disease as assessed by an ophthalmic examination. Doxycycline (10 or 20 mg\/kg [4.5 or 9.1 mg\/lb]) was administered orally every 24 hours for 4 days. Tear and plasma samples were collected at fixed time points, and doxycycline concentration was assessed by means of liquid chromatography\u2013tandem mass spectrometry. Concentration-time data were calculated via noncompartmental analysis.<\/jats:p>\n<jats:p><jats:bold>Results<\/jats:bold>\u2014Following administration of doxycycline (10 mg\/kg\/d, PO), maximum plasma doxycycline concentration was 2.2 \u03bcg\/mL at 6.1 hours on day 1 and was 1.5 \u03bcg\/mL at 4.0 hours on day 4. Administration of doxycycline (20 mg\/kg\/d, PO) produced a maximum plasma doxycycline concentration of 2.4 \u03bcg\/mL at 2.3 hours on day 1 and 1.9 \u03bcg\/mL at 5.8 hours on day 4. Doxycycline elimination half-life on day 4 in animals receiving doxycycline at a dosage of 10 or 20 mg\/kg\/d was 6.7 or 5.6 hours, respectively. Mean plasma-to-tear doxycycline concentration ratios over all days were not significantly different between the low-dose (9.85) and high-dose (9.83) groups. For both groups, doxycycline was detectable in tears for at least 6 days following cessation of dosing.<\/jats:p>\n<jats:p><jats:bold>Conclusions and Clinical Relevance<\/jats:bold>\u2014Oral administration of doxycycline at the doses tested in the present study resulted in concentrations in the plasma and tears of northern elephant seals likely to be clinically effective for treatment of selected cases of systemic infectious disease, bacterial ulcerative keratitis, and ocular surface inflammation. This route of administration should be considered for treatment of corneal disease in northern elephant seals and possibly other related pinniped species.<\/jats:p>","DOI":"10.2460\/javma.243.8.1170","type":"journal-article","created":{"date-parts":[[2013,10,4]],"date-time":"2013-10-04T14:41:23Z","timestamp":1380897683000},"page":"1170-1178","source":"Crossref","is-referenced-by-count":13,"title":["Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration"],"prefix":"10.2460","volume":"243","author":[{"given":"Kate S.","family":"Freeman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M.","family":"Thomasy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Stanley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Van Bonn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Gulland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari S.","family":"Friedlaender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Maggs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"Vet Ophthalmol","first-page":"390","article-title":"Characterization of \u201csea lion keratitis\u201d in captive Zalophus californianus","volume":"12","author":"Colitz","year":"2010"},{"key":"ref2","series-title":"Invest Ophthalmol Vis Sci","first-page":"2544","article-title":"Doxycycline inhibition of interleukin-1 in the corneal epithelium","volume":"41","author":"Solomon","year":"2000"},{"key":"ref3","series-title":"Vet Ophthalmol","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1111\/j.1463-5224.2008.00662.x","article-title":"Doxycycline levels in preocular tear film of horses following oral administration","volume":"11","author":"Baker","year":"2008"},{"key":"ref4","series-title":"Korean J Ophthalmol","doi-asserted-by":"publisher","first-page":"258","DOI":"10.3341\/kjo.2005.19.4.258","article-title":"The effect of low-dose doxycycline therapy in chronic meibomian gland dysfunction","volume":"19","author":"Yoo","year":"2005"},{"key":"ref5","series-title":"Vet J","first-page":"380","article-title":"Pharmacokinetics of doxycycline in sheep after intravenous and oral administration","volume":"180","author":"Castro","year":"2009"},{"key":"ref6","series-title":"Plumb's veterinary drug handbook","first-page":"1187","author":"Plumb","year":"2011"},{"key":"ref7","series-title":"CRC handbook of marine mammal medicine","first-page":"314","article-title":"Bacterial diseases of cetaceans and pinnipeds","author":"Dunn","year":"2001"},{"key":"ref8","series-title":"J Wild Dis","doi-asserted-by":"publisher","first-page":"426","DOI":"10.7589\/0090-3558-41.2.426","article-title":"Leptospirosis in northern elephant seals (Mirounga angustirostris) stranded along the California coast","volume":"41","author":"Colegrove","year":"2005"},{"key":"ref9","series-title":"Vet Q","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1080\/01652176.2006.9695204","article-title":"An outbreak of leptospirosis in seals (Phoca vitulina) in captivity","volume":"28","author":"Kik","year":"2006"},{"key":"ref10","series-title":"Dis Aquat Organ","first-page":"81","article-title":"Health risks for marine mammal workers","volume":"19","author":"Hunt","year":"2008"},{"key":"ref11","series-title":"Vet Res","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1051\/vetres:2008036","article-title":"Bartonella species detection in captive, stranded and free-ranging cetaceans","volume":"39","author":"Harms","year":"2008"},{"key":"ref12","series-title":"Statement for the use of animals in ophthalmic and visual research","year":"2009"},{"key":"ref13","series-title":"Vet Ophthalmol","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1111\/j.1463-5224.2011.00984.x","article-title":"Pharmacokinetics of famciclovir and penciclovir in tears following oral administration of famciclovir to cats: a pilot study","volume":"15","author":"Thomasy","year":"2012"},{"key":"ref14","series-title":"J Chromatogr A","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.chroma.2005.08.027","article-title":"Simultaneous extraction and analysis of 11 tetracycline and sulfonamide antibiotics in influent and effluent domestic wastewater by solid-phase extraction and liquid chromatography-electrospray ionization tandem mass spectrometry","volume":"1097","author":"Yang","year":"2005"},{"key":"ref15","series-title":"Acta Vet Hung","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1556\/004.49.2001.1.5","article-title":"Pharmacokinetics and bioavailability of doxycycline in fasted and nonfasted broiler chickens","volume":"49","author":"Laczay","year":"2001"},{"key":"ref16","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"310","DOI":"10.2460\/ajvr.67.2.310","article-title":"Pharmacokinetics and tissue distribution of doxycycline after oral administration of single and multiple doses in horses","volume":"67","author":"Davis","year":"2006"},{"key":"ref17","series-title":"J Vet Pharmacol Ther","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1111\/j.1365-2885.2004.00602.x","article-title":"Volumes of distribution","volume":"27","author":"Toutain","year":"2004"},{"key":"ref18","series-title":"J Vet Pharmacol Ther","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1111\/j.1365-2885.2007.00932.x","article-title":"Pharmacokinetics of pra-dofloxacin and doxycycline in serum, saliva and tear fluid in cats after oral administration","volume":"31","author":"Hartmann","year":"2008"},{"key":"ref19","series-title":"J Vet Pharmacol Ther","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1111\/j.1365-2885.1990.tb00797.x","article-title":"Comparative pharmacokinetics of doxycycline in cats and dogs","volume":"13","author":"Riond","year":"1990"},{"key":"ref20","series-title":"Aquat Mamm","first-page":"1","article-title":"The significance of eyelid glands in delphinids","volume":"6","author":"Waller","year":"1978"},{"key":"ref21","series-title":"CRC handbook of marine mammal medicine","first-page":"920","article-title":"Seals and sea lions","author":"Gulland","year":"2001"},{"key":"ref22","series-title":"Am J Ophthalmol","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/S0002-9394(03)00890-0","article-title":"Ocular rosacea in childhood","volume":"137","author":"Nazir","year":"2004"},{"key":"ref23","series-title":"J Zoo Wildl Med","first-page":"171","article-title":"Bacterial isolates from California sea lions (Zalophus californianus), harbor seals (Phoca vitulina), and northern elephant seals (Mirounga angustirostris) admitted to a rehabilitation center along the central California coast, 1994\u20131995","volume":"29","author":"Thornton","year":"1998"},{"key":"ref24","series-title":"Jpn J Ophthalmol","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/s10384-008-0511-4","article-title":"A case of Vibrio vulnificus keratitis","volume":"52","author":"You","year":"2008"},{"key":"ref25","series-title":"Acta Vet (Beograd)","first-page":"309","article-title":"Inhibitory and mycoplasmacidal concentrations of some antibiotic on strains of Mycoplasma mycoides subsp. mycoides SC: the causative agent of contagious bovine pleuropneumoniae","volume":"48","author":"Egwu","year":"1998"},{"key":"ref26","series-title":"Int J Antimicrob Agents","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.ijantimicag.2003.11.006","article-title":"Prevention of the selection of resistant Staphylococcus aureus by moxifloxacin plus doxycycline in an in vitro dynamic model: an additive effect of the combination","volume":"23","author":"Firsov","year":"2004"},{"key":"ref27","series-title":"Diagn Microbiol Infect Dis","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.diagmicrobio.2004.08.003","article-title":"Quality Control Working Group. MIC quality control guidelines for doxycycline when testing gram-positive control strains by the reference methods","volume":"50","author":"Ross","year":"2004"},{"key":"ref28","series-title":"Int J Antimicrob Agents","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/S0924-8579(01)00464-2","article-title":"In vitro resistance of Bacillus anthracis Sterne to doxycycline, macrolides and quinolones","volume":"18","author":"Brook","year":"2001"},{"key":"ref29","series-title":"Antimicrob Agents Chemother","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1128\/AAC.47.6.1867-1874.2003","article-title":"Antimicrobial resistance in respiratory tract Streptococcus pneumoniae isolates: results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002","volume":"47","author":"Zhanel","year":"2003"},{"key":"ref30","series-title":"Microbiol Immunol","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/j.1348-0421.1998.tb01971.x","article-title":"In vitro susceptibility of Chlamydia pecorum to macrolides, tetracyclines, quinolones and beta-lactam","volume":"42","author":"Pudjiatmoko","year":"1998"},{"key":"ref31","series-title":"Clin Infect Dis","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1086\/516284","article-title":"Pharmacokinetic\/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men","volume":"26","author":"Craig","year":"1998"},{"key":"ref32","series-title":"Int J Antimicrob Agents","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.ijantimicag.2007.11.011","article-title":"Pharmacodynamics of doxycycline for chemoprophylaxis of Lyme disease: preliminary findings and possible implications for other antimicrobials","volume":"31","author":"Lee","year":"2008"},{"key":"ref33","series-title":"J Am Vet Med Assoc","doi-asserted-by":"publisher","first-page":"390","DOI":"10.2460\/javma.230.3.390","article-title":"Na\u00efve averaged, na\u00efve pooled, and population pharmacokinetics of orally administered marbofloxacin in juvenile harbor seals","volume":"230","author":"KuKanich","year":"2007"},{"key":"ref34","series-title":"J Vet Intern Med","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1939-1676.2010.0654.x","article-title":"2010 ACVIM small animal consensus statement on leptospirosis: diagnosis, epidemiology, treatment, and prevention","volume":"25","author":"Sykes","year":"2011"},{"key":"ref35","series-title":"Saunders handbook of veterinary drugs","first-page":"858","author":"Papich","year":"2007"},{"key":"ref36","series-title":"Br J Ophthalmol","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1136\/bjo.2007.125989","article-title":"Does orally administered doxycycline reach the tear film?","volume":"92","author":"Smith","year":"2008"},{"key":"ref37","series-title":"Pharmacol Res","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/j.phrs.2011.06.013","article-title":"The non-antibiotic properties of tetracyclines: clinical potential in ophthalmic disease","volume":"64","author":"Federici","year":"2011"},{"key":"ref38","series-title":"Pharmacol Res","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.phrs.2010.10.007","article-title":"Clinical applications of non-antimicrobial tetracyclines in dermatology","volume":"63","author":"Monk","year":"2011"}],"container-title":["Journal of the American Veterinary Medical Association"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/javma\/243\/8\/javma.243.8.1170.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/javma\/243\/8\/javma.243.8.1170.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/javma\/243\/8\/javma.243.8.1170.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T11:41:13Z","timestamp":1741347673000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/javma\/243\/8\/javma.243.8.1170.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,15]]},"references-count":38,"journal-issue":{"issue":"8"},"URL":"https:\/\/doi.org\/10.2460\/javma.243.8.1170","relation":{},"ISSN":["0003-1488"],"issn-type":[{"value":"0003-1488","type":"print"}],"subject":[],"published":{"date-parts":[[2013,10,15]]}}}