Abstract

Sea turtles endure wounds, entanglements, fractures or other presumed painful or inflammatory conditions. Currently, there are no pharmacokinetic studies on analgesic or anti-inflammatory drugs (NSAIDs) in any chelonian species. In the absence of these studies to allow formulation of dosing protocols, dosages have been extrapolated from pharmacokinetic studies in mammals and birds. Data on meloxicam, a cyclooxygenase-1 sparing NSAID, in small animals, birds and lizards suggests a good safety profile and efficacy in clinical trials and experimental studies. Therefore, this study was conducted to investigate the pharmacokinetics of intravenous (IV) administration of meloxicam in loggerhead sea turtles (Caretta caretta). The purpose of this study was to establish baseline pharmacokinetic features of meloxicam after an IV dose which could be used to plan oral and IM studies. Seven healthy, sub-adult to adult sized turtles were administered 0.2 mg/kg of meloxicam intravenously in the right external jugular vein. Serial blood samples were collected prior to, and up to 96 hours post injection. Environmental and body temperatures were measured after each sample collection. Plasma was harvested by centrifugation and stored at -80°F prior to analysis via reverse-phase high performance liquid chromatography (HPLC). A computer program (WinNonlin, Version 5.0, Pharsight Corporation, Mountain View, CA) was used to determine pharmacokinetic parameters. Both two- and three-compartment models were fitted to the data. For each analysis, there were severe outliers and high variability among some parameters. Therefore, a non-compartmental analysis was performed that did not assume any compartmental structure. In this analysis, the mean half-life (harmonic mean) was 7.25 hours, the volume of distribution at steady-state (VD_SS) was 201.1 (±287.3) mL/kg, and the systemic clearance was 19.2 (±4.3) mL/kg/hr. Mean residence time (MRT) was 10.5 (± 14.2) hours. The low VD_SS is consistent with NSAIDs in other species and is attributed to high protein binding. The clearance in turtles was higher than reported for dogs.

The half-life observed in these animals was also faster than in dogs, which is probably a result of the higher clearance. In conclusion, an HPLC assay for meloxicam in loggerhead sea turtles was successfully developed, and basic pharmacokinetic parameters following an IV dose were established. The relatively rapid elimination rate and clearance may necessitate higher doses and/or more frequent intervals to maintain effective plasma concentrations. These data will be used for additional studies with oral and IM doses.