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

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. 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. (J Am Vet

A Framework for Meta-Analysis of Veterinary Drug Pharmacokinetic Data Using Mixed Effect Modeling

“…One objective of the NLME model approach is to identify the appropriate covariates affecting the PK properties of a subpopulation and to explain the intersubject and intrasubject variability in terms of these covariates, which is helpful to optimize the initial dosage regimen to meet the therapeutic window and safety criterion of a certain subpopulation of animals …”

The presence of minocycline in the tear film of normal horses following oral administration and its anticollagenase activity

“…As was previously reported for doxycycline in the tear film of horses and elephant seals, there was significant variability between subjects (Fig. b) …”

“…The lacrimal gland and gland of the third eyelid are the biggest contributors of aqueous tears in dogs and horses . In the case of minocycline and doxycycline, it is thought that the increased lipophilicity of these compounds concentrates these molecules in secretory glands such as the lacrimal gland . Previous studies have identified the continuous release of drug into the tear film past its plasma half‐life due to this concentration .…”

“…Research demonstrating that orally administered doxycycline is secreted into the tear film and concentrates in the lacrimal glands showed promise as an alternative to traditional topical therapy . Due to lower plasma protein binding of doxycycline in horses, horses specifically appear to have a higher C max of doxycycline in their tears relative to other studied species . These findings prompted use of oral doxycycline as an anticollagenase and antimicrobial treatment against keratitis, most frequently in the emergent management of a rapidly progressing melting ulcer.…”

PHARMACOKINETICS OF SINGLE-DOSE ORALLY ADMINISTERED CIPROFLOXACIN IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS)

“…25 Although a variety of antibiotics are commonly used in pinniped species, information on pharmacokinetics of these drugs remains scarce, with only a handful of studies thus far published. 11,12,19,22 The Marine Mammal Center (TMMC) is a rehabilitation facility that cares for roughly 600 ill and injured marine mammals each year, approximately 60% of which are California sea lions (Zalophus californianus). Ciprofloxacin is currently one of the most frequently administered antibiotics at TMMC, and is commonly used for treatment of California sea lions affected by a variety of bacterial infections, including pneumonia, leptospirosis, and infected traumatic injuries, at a dosage of 5-10 mg/kg p.o.…”