Pharmacokinetic Parameters and Tissue Withdrawal Intervals for Sheep Administered Multiple Oral Doses of Meloxicam.

Sarah Depenbrock,Lisa A. Tell,Jessie Ziegler,Maaike O. Clapham,Tara Urbano,Scott Wetzlich

doi:10.3390/ani11102797

Abstract

Simple SummaryMeloxicam is an anti-inflammatory drug used to treat pain and inflammation in ruminants including sheep, and pharmacokinetic studies are needed to protect the food supply from drug residues after use in food-producing animals. This study estimated plasma pharmacokinetic parameters and meat withdrawal intervals (WDI) for market sheep after multiple daily oral doses of meloxicam. Single and multiple dose plasma pharmacokinetic studies, a multi-dose tissue depletion study, and a follow-up study to investigate if events prior to slaughter were associated with differences in plasma meloxicam concentrations, all using sample data collected after completion of dosing, were completed. Using regulatory agency methods for calculating withdrawal times, an estimated WDI of at least 10 d following the last dose is recommended for market lambs treated with ten daily oral 1 mg/kg doses of meloxicam tablets suspended in water. The effect of events surrounding slaughter on plasma meloxicam concentrations in lambs is unknown but should be considered if plasma samples are obtained immediately prior to or during the slaughter process and used for pharmacokinetic investigations.Meloxicam is an anti-inflammatory drug used to treat pain and inflammation in ruminants including sheep, and pharmacokinetic studies are needed to protect the food supply from drug residues after use in food-producing animals. This study estimated plasma pharmacokinetic parameters and meat withdrawal intervals (WDI) for market sheep after multiple daily oral doses of meloxicam. Single and multiple dose plasma pharmacokinetic studies, a multi-dose tissue depletion study, and a follow-up study to investigate if events prior to slaughter were associated with differences in plasma meloxicam concentrations, all using sample data collected after completion of dosing, were completed. Using regulatory agency methods for calculating withdrawal times, an estimated WDI of at least 10 d following the last dose is recommended for market lambs treated with 10 daily oral 1 mg/kg doses of meloxicam tablets suspended in water. The effect of events surrounding slaughter on plasma meloxicam concentrations in lambs is unknown but should be considered if plasma samples are obtained immediately prior to or during the slaughter process and used for pharmacokinetic investigations.

Highlights

Pain and inflammation can be caused by disease states or some routine management practices such as castration or tail docking in sheep
After portions completion of experimental the live animal sampling protocols, between animal enrollments in different of the design is illustrated in remaining sheep were either returned to the facility flock or sent through slaughter accredited slaughter facility determined by theresidue study depletion protocol. sampling, All procedures were approved by theprotocol
Pharmacokinetic parameters estimated from plasma sample concentrations versus time from the live animal pharmacokinetic studies are displayed in Tables 2 and 3

Summary

Introduction

Pain and inflammation can be caused by disease states or some routine management practices such as castration or tail docking in sheep. A study investigating lameness in sheep demonstrated that a single 1.0 mg/kg IV dose alleviated some experimentally induced signs of inflammation, the associated plasma meloxicam concentration relative to the effective dose in 50% of the study population (ED50) was not reported [2]. Pharmacokinetic parameters for sheep receiving a single oral dose of meloxicam as 15 mg tablets have been described with a 72% bioavailability and serum concentrations remaining above 1 μg/mL for over 12 h [6]. Injectable meloxicam formulations have been associated with decreases in pain and inflammation in sheep [1,2] no median effective (ED50) dose has been established for sheep. Plasma concentrations after repeated oral meloxicam dosing of sheep are lacking

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Discussion

Conclusion