Abstract

During corneal ulceration, matrix metalloproteinases facilitate dissolution of stromal collagen known as malacia. Doxycycline and minocycline have anticollagenase activity, accumulate in lacrimal and meibomian glands, and are effective in managing corneal diseases.¹ In cetaceans, ocular secretions are produced by Harderian glands. No true meibomian glands are present, resulting in a lack of a lipid layer within the tear film.² While this may prohibit excretion of lipophilic tetracyclines, previous studies suggest possible drug accumulation in Harderian glands.³ This study aims to determine and compare tear and plasma concentrations of doxycycline and minocycline following oral administration in bottlenose dolphins (Tursiops truncatus) using a population pharmacokinetic design. Both drugs are hypothesized to reach detectable tear concentrations, with minocycline having a significantly longer half-life, higher plasma concentrations, and higher tear:plasma concentration ratios than doxycycline, as minocycline is more lipophilic and less protein-bound. Twenty-six dolphins at SeaWorld San Diego have received minocycline (2 mg/kg) or doxycycline (2 mg/kg) once orally in a randomized crossover design. Tear and plasma was sampled at specified intervals for complete pharmacokinetic profile analysis. Drug concentration is measured using high-pressure liquid chromatography and analyzed using nonlinear mixed modeling. Study results will determine if oral administration of doxycycline or minocycline result in higher tear film concentrations to be effective in ocular surface disease management. Oral medications that can reach effective tear concentrations have additional potential clinical benefits compared to topical treatments for animals living in an aquatic environment. Results also provide guidance on drug preference and appropriate dosing for routine treatment.

Acknowledgements

The authors wish to thank Drs. Judy St. Leger, Rebecca Rivera, Ms. Jennifer Rego, Mrs. Jennifer Haselow, Patricia Alley, Joy Brackbill, Kim Regan, and Melinda Tucker of SeaWorld San Diego, Ms. Heather Halsey of Veterinary Specialty Hospital San Diego, Ms. Delta Dise and the laboratory technicians at North Carolina State University, Dr. Hendrik Nollens of SeaWorld Parks and Entertainment, as well as the animal training staff at SeaWorld San Diego for their help and support.

* Presenting author
+ Student presenter

Literature Cited

1.  Papich MG, Riviere MG. 2018. Tetracycline antibiotics. In: Riviere MG, Papich MG, eds. Veterinary Pharmacology and Therapeutics, 10th ed. Ames, IA: Wiley-Blackwell.

2.  Tarpley RJ, Ridgway SH. 1991. Orbital gland structure and secretions in the Atlantic bottlenose dolphin (Tursiops truncatus). J Morphol. 207:173–184.

3.  Freeman KS, Thomasy SM, Stanley SD, et al. 2013. Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration. J Am Vet Med Assoc. 243:1170–1178.