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. 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-tandem mass spectrometry. Concentration-time data were calculated via noncompartmental analysis.

Results

Following administration of doxycycline (10 mg/kg/d, PO), maximum plasma doxycycline 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 doxycycline 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.

The Marine Mammal Center (TMMC) cares for malnourished California sea lion (CSL) (Zalophus californianus) pups and yearlings every year. Hypoglycemia is a common consequence of malnutrition in young CSLs. Administering dextrose during a hypoglycemic crisis is vital to recovery. Traditional veterinary approaches to treat hypoglycemia pose therapeutic challenges in otariids, as vascular access and catheter maintenance can be difficult. The current approach to a hypoglycemic episode at TMMC is to administer dextrose intravenously (i.v.) by medically trained personnel. Intraperitoneal (i.p.) dextrose administration is an attractive alternative to i.v. administration because volunteer staff with basic training can administer treatment instead of waiting for trained staff to treat. This study compares the effects of i.v., i.p., and no dextrose administration on serum glucose and insulin in clinically healthy, euglycemic CSL yearlings. Three groups of animals, consisting of five sea lions each, were treated with 500 mg/kg dextrose using one of the following routes: i.v., i.p., or no dextrose (control). A jugular catheter was placed, and blood samples were collected at times 0, 5, 15, 30, 60, 120, 180, and 240 min after dextrose administration. I.v. dextrose administration resulted in an increase of serum glucose concentrations from a baseline level of approximately 150 mg/dl to a peak of approximately 350 mg/dl. The resulting hyperglycemia persisted for approximately 2 hr and was associated with an attenuated plasma insulin response compared with most terrestrial mammals. Intraperitoneal dextrose administration resulted in increases of serum glucose to approximately 200 mg/dl, which gradually declined to baseline by 2 hr after dextrose administration. These data suggest that the initial treatment of a hypoglycemic crisis in young malnourished CSLs can be accomplished with i.p. dextrose, thus enabling minimally trained volunteer staff to respond immediately to a crisis. Further studies are needed to determine the most appropriate long-term treatment.