Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration

Kate S. Freeman, Sara M Thomasy, Scott D Stanley, William Van Bonn, Frances Gulland, Ari S. Friedlaender, David J Maggs

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Objective-To assess tear and plasma concentrations of doxycycline following oral administration to northern elephant seals (Mirounga angustirostris). Design-Pharmacokinetic study. Animals-18 juvenile northern elephant seals without signs of ocular disease. Procedures-Study seals were receiving no medications other than a multivitamin and were free from signs of ocular disease as assessed by an ophthalmic examination. Doxy-cycline (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-tandem mass spectrometry. Concentration-time data were calculated via noncompartmental analysis. Results-Following administration of doxycycline (10 mg/kg/d, PO), maximum plasma doxy-cycline concentration was 2.2 μg/mL at 6.1 hours on day 1 and was 1.5 μg/mL at 4.0 hours on day 4. Administration of doxycycline (20 mg/kg/d, PO) produced a maximum plasma doxy-cycline concentration of 2.4 μg/mL at 2.3 hours on day 1 and 1. 9 μg/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. Conclusions and Clinical Relevance-Oral 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.

Original languageEnglish (US)
Pages (from-to)1170-1178
Number of pages9
JournalJournal of the American Veterinary Medical Association
Volume243
Issue number8
DOIs
StatePublished - Oct 15 2013

ASJC Scopus subject areas

  • veterinary(all)

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