Pharmacokinetics of the analgesic and anti-inflammatory drug meloxicam after administration of multiple doses to nursehound sharks (Scyliorhinus stellaris)

Abstract

Objective: To determine the pharmacokinetics of meloxicam in the nursehound shark (Scyliorhinus stellaris) during multiple dose administration.

Study design: Prospective experimental trial.

Animals: A total of eight clinically healthy adult nursehounds (four males, four females).

Methods: Meloxicam was administered intramuscularly at a dose of 1.5 mg kg^-1 once daily for 7 days. Blood samples were collected from the caudal vein for pharmacokinetic analysis at 2.5 hours and 24 hours after drug administration. After a 4 week washout period, meloxicam was administered orally at the same dose at 12 hour intervals for three repeated doses. Blood samples were collected at 1, 2, 4, 6, 8, 12, 24, 36 and 48 hours after the first administration. Sharks were visually monitored during each study and 4 weeks afterwards for side effects or signs of toxicity. Time required to achieve steady state was assessed by visual inspection and statistical comparison of peak and trough concentrations using a Friedman test; comparison between sexes was performed using a Mann-Whitney U test and p-value was set at 0.05.

Results: No animal died or showed clinical signs of toxicity during the study. Meloxicam administered orally did not produce detectable concentrations in plasma. After intramuscular administration, steady state was achieved after five doses, and mean trough and peak plasma concentrations at steady state were 1.76 ± 0.21 μg mL^-1 and 3.02 ± 0.23 μg mL^-1, respectively. Mean peak concentration accumulation ratio was 2.50 ± 0.22.

Conclusions and clinical relevance: This study shows that intramuscular posology produces plasma concentrations considered therapeutic for other species. However, meloxicam was not detected in plasma after oral administration. These results suggest that meloxicam administered intramuscularly may be a useful non-steroid anti-inflammatory drug in nursehound sharks. Further pharmacodynamic studies are needed to fully evaluate its clinical use in this species.

Keywords: NSAID; analgesia; drug kinetics; elasmobranch; meloxicam; plasma.