Comparative Pharmacokinetics and Tissue Concentrations of Flunixin Meglumine and Meloxicam in Tilapia (Oreochromis spp.)

Abstract

Evidence of pain perception in fish is well established, but analgesic use in aquaculture is limited. The objective was to investigate the comparative pharmacokinetics of flunixin administered intramuscularly (IM) and meloxicam administered IM or orally (PO) in tilapia. Two hundred and seventy fish were assigned to 1 of 3 treatment groups: flunixin meglumine IM (2.2 mg/kg); meloxicam IM (1 mg/kg); or meloxicam PO (1 mg/kg). Blood and tissue samples were collected from 6 fish per treatment at 14 time points for 10 days. Drug concentrations were determined using ultra-high-pressure liquid chromatography coupled with mass spectroscopy. Plasma concentration versus time data were analyzed with a non-compartmental approach using a commercially available software. Flunixin reached a mean maximum concentration (Cmax) of 4826.7 ng/mL at 0.5 h, had a terminal half-life (T1/2) of 7.34 h, and an area under the concentration–time curve extrapolated to infinity (AUCINF_obs) of 25,261.62 h·ng/mL. Meloxicam IM had a T1/2 of 9.4 h after reaching a Cmax of 11.3 ng/mL at 2 h, with an AUCINF_obs of 150.31 h·ng/mL. Meloxicam PO had a T1/2 of 1.9 h after reaching a Cmax of 72.2 ng/mL at 2 h, with an AUCINF_obs of 400.83 h·ng/mL. Tissue concentrations of both drugs were undetectable by 9 h. Flunixin reached a sufficient plasma concentration to potentially have an analgesic effect, while meloxicam, when administered at the given dosage, likely would not.