Comparative Pharmacokinetics of a Single Dose of Meloxicam in the California Sea Lion (Zalophus californianus) and Pacific Harbor Seal (Phoca vitulina richardii)
Abstract
The non-steroidal anti-inflammatory drug (NSAID) meloxicam is a widely used analgesic in pinniped medicine and surgery. Meloxicam pharmacokinetics studies have demonstrated considerable variability across species, lasting from hours in some avian species to multiple days in bottlenose dolphins (Tursiops truncatus).1,2 Given the importance of balancing adequate analgesia against potential adverse effects,3-6 investigation into the appropriate dose for pinniped patients is indicated. Rehabilitated, pre-release, and apparently healthy Pacific harbor seals (PHS; n=17) and California sea lions (CSL; n=13) were enrolled into a sparse-sampling, population-based pharmacokinetic study. Each animal was administered a single oral dose of meloxicam at 0.1 mg/kg and two blood samples were collected from each animal at varying intervals over the following 96 hours. Plasma concentrations were determined by high-pressure liquid chromatography at the Clinical Pharmacology Laboratory at North Carolina State University, College of Veterinary Medicine. Data was analyzed using Phoenix nonlinear mixed effects modeling. In PHS, peak plasma concentration (Cmax) was 0.33 µg/mL with a half-life (Ke T½) of 31.53 hours and area under the curve (AUC) was 17.85 µg*h/mL. In CSL, Cmax was 0.17 µg/mL with Ke T½ of 32.71 hours and AUC 9.89 µg*h/mL. Although the therapeutic plasma concentration of meloxicam in pinnipeds is unknown, a concentration of 0.13–0.88 µg/mL is described to have clinical benefits in other species.7-10 Given the analysis, every day dosing may not be necessary for these two species of pinnipeds, although further research into multi-dosing, marine mammal inflammatory pathways, and the effects of NSAID therapy are warranted.
Acknowledgements
The funding for this project was made possible through the Morris Animal Foundation, Pilot Study Grant #D21ZO-803. Samples were collected under TMMC IACUC# 2021-3-1, and animal rehabilitation was permitted by NOAA Fisheries, permit #18786. Animal care and welfare was expertly provided by the dedicated volunteer and animal care staff at The Marine Mammal Center. We are particularly grateful to Carlos Rios and Jesierose Poblacion for their assistance with sample processing.
*Presenting author
Literature Cited
1. Herrick KES, Papich MG, Croft LA, Schmitt TL. Pharmacokinetics of single dose piroxicam in bottlenose dolphins. In: IAAAM 2017 Annual Conference Proceedings. Cancun, Mexico; 2017.
2. Simeone CA, Nollens HH, Meegan JM, Schmitt TL, Jensen ED, Papich MG, Smith CR. Pharmacokinetics of single dose oral meloxicam in bottlenose dolphins (Tursiops truncatus). J Zoo Wildl Med. 2014;45(3):594–599.
3. Ross K, Le-Bert C, Ix JH, Ardente A, Stacy N, Jensen E. Treatment of acute kidney injury following meloxicam administration in an Atlantic bottlenose dolphin (Tursiops truncatus). In: IAAAM 2022 Annual Conference Proceedings. 2022.
4. Eskafian H, Tabrizi AS, Lari MA. Gastroscopic study of meloxicam, tramadol, and their combined administration on the development of gastric injuries in dogs. Top Companion Anim Med. 2017;32(3):109–113.
5. Lipscomb GR, Wallis N, Armstrong G, Rees WDW. Gastrointestinal tolerability of meloxicam and piroxicam: a double-blind placebo-controlled study. Br J Clin Pharmacol. 1998;46(2):133–137.
6. Noble G, Edwards S, Lievaart J, Pippia J, Boston R, Raidal SL. Pharmacokinetics and safety of single and multiple oral doses of meloxicam in adult horses. J Vet Intern Med. 2012;26(5):1192–1201.
7. Toutain PL, Cester CC. Pharmacokinetic-pharmacodynamic relationships and dose response to meloxicam in horses with induced arthritis in the right carpal joint. Am J Vet Res. 2004;65(11):1533–1541.
8. Giraudel JM, Diquelou A, Laroute V, Lees P, Toutain PL. Pharmacokinetic/pharmacodynamic modelling of NSAIDs in a model of reversible inflammation in the cat. Br J Pharmacol. 2005;146(5):642–653.
9. Jeunesse EC, Bargues IA, Toutain CE, Lacroix MZ, Letellier IM, Giraudel JM, Toutain PL. Paw inflammation model in dogs for preclinical pharmacokinetic/pharmacodynamic investigations of nonsteroidal anti-inflammatory drugs. J Pharmacol Exp Ther. 2011;338(2):548–558.
10. Lees P, Giraudel J, Toutain PL, Pelligand L, King JN. PK-PD integration and PK- PD modelling of preferential and selective COX-2 inhibitors: towards safer drugs and improved dosage regimens. J Vet Pharmacol Ther. 2009;32:33–36.