Does Orally Administered Doxycycline Achieve Adequate Concentration in the Plasma and Tears of Elephant Seals (Mirounga angustirostris)?
Kate S. Freeman1, MEM, DVM; Sara M. Thomasy2, DVM, PhD, DACVO; Scott D. Stanley3, PhD; William Van Bonn4, DVM; Frances M.D. Gulland4, PhD, Vet MB, MRCVS; Ari S. Friedlaender5, PhD; David J. Maggs2, BVSc, DACVO
1Veterinary Medical Teaching Hospital, University of California, Davis, CA, USA; 2Department of Surgical and Radiological Sciences, University of California, Davis, CA, USA; 3K.L. Maddy Equine Analytical Chemistry Laboratory, University of California, Davis, CA, USA; 4The Marine Mammal Center, Sausalito, CA, USA; 5Marine Laboratory, Duke University, Beaufort, NC, USA
Keratitis, a common, painful, and potentially blinding disease of pinnipeds, frequently involves bacterial infection as either a primary or secondary factor. Topical antimicrobial treatment is rarely an option due to animal lifestyle and temperament. This project assessed plasma and tear doxycycline concentrations following oral doxycycline (doxycycline hyclate, Medisca Pharmaceuticals, Las Vegas, NV, USA) administration to elephant seals. The study involved eighteen juvenile elephant seals without ocular disease who were housed at The Marine Mammal Center. Doxycycline (10 or 20 mg/kg) was administered orally every 24 hours for four days. Tear and plasma samples were collected at fixed times, and doxycycline concentration assessed using liquid chromatography/mass spectrometry. Concentration-time data was calculated using noncompartmental analysis. Following administration of 10 mg/kg/day doxycycline, maximum plasma doxycycline concentration (Cmax) on day 4 was 1.5 µg/ml at 4.0 hours. Administration of 20 mg/kg/day doxycycline produced Cmax on day 4 of 1.9 µg/ml at 5.8 hours. Doxycycline elimination half-life on day 4 in animals receiving 10 or 20 mg/kg/day doxycycline was 6.7 or 5.6 hours, respectively. Plasma:tear doxycycline concentrations averaged over all days were not significantly different between the low-dose (9.85) and high-dose (9.83) groups (p=0.99). Doxycycline was detectable in tears for at least six days following cessation of oral dosing. Doxycycline administered orally to elephant seals at these doses achieved concentrations in tears and plasma likely to have some antimicrobial and anti-inflammatory effects at the ocular surface and systemically. It should be considered for treatment of corneal disease in this and possibly, other similar species.
The authors thank Helen Kado-Fong, Dr. Lauren Smith, Dr. Nicola Pussini, Ben Im, Ryen Morey, Marion Fischer, and Kim Calloway for technical assistance.