Pharmacokinetic Parameters and Estimating Extra-Label Tissue Withdrawal Intervals Using Three Approaches and Various Matrices for Domestic Laying Chickens Following Meloxicam Administration.

Emily D Richards,Scott E Wetzlich,Zhoumeng Lin,Maaike O Clapham,Nathaniel C Burmas,Lisa A Tell,Jennifer L Davis,Rachel S Dutch

doi:10.3389/fvets.2022.826367

Abstract

Meloxicam is commonly prescribed for treating chickens in backyard or small commercial operations despite a paucity of scientific data establishing tissue withdrawal interval recommendations following extra-label drug use (ELDU). Historically, ELDU withdrawal intervals (WDIs) following meloxicam administration to chickens have been based on the time when meloxicam concentrations fall below detectable concentrations in plasma and egg samples. To date, no studies have addressed tissue residues. ELDU WDIs are commonly calculated using terminal elimination half-lives derived from pharmacokinetic studies. This study estimated pharmacokinetic parameters for laying hens following meloxicam administration and compared ELDU WDIs calculated using tissue terminal elimination half-lives vs. those calculated using FDA tolerance and EMA's maximum regulatory limit statistical methods, respectively. In addition, ELDU WDIs were calculated using plasma meloxicam concentrations from live birds to determine if plasma data could be used as a proxy for estimating tissue WDIs. Healthy domestic hens were administered meloxicam at 1 mg/kg intravenous (IV) once, 1 mg/kg orally (PO) once daily for eight doses or 1 mg/kg PO twice daily for 20 doses. Analytical method validation was performed and meloxicam concentrations were quantified using high-performance liquid chromatography. In general, the terminal elimination technique resulted in the longest ELDU WDIs, followed by the FDA tolerance and then EMA's maximum residue limit methods. The longest ELDU WDIs were 72, 96, and 384 (or 120 excluding fat) h for the IV, PO once daily for eight doses, and PO twice daily for 20 doses, respectively. Plasma data are a possible dataset for estimating a baseline for tissue ELDU WDI estimations when tissue data are not available for chickens treated with meloxicam. Finally, pharmacokinetic parameters were similar in laying hens to those published for other avian species.

Highlights

Extra-label drug use (ELDU) in backyard chickens is a common practice since there are few Food and Drug Administration (FDA) approved medications for administration to individual birds or small flocks [1, 2]
The data from our study were used to estimate pharmacokinetic parameters for meloxicam administered to laying hens and were similar compared to other bird species
Results from this study suggest that plasma data can be used as a baseline for estimating tissue extra-label drug use (ELDU) withdrawal interval (WDI) when meloxicam is administered to laying chickens

Summary

Introduction

Extra-label drug use (ELDU) in backyard chickens is a common practice since there are few Food and Drug Administration (FDA) approved medications for administration to individual birds or small flocks [1, 2]. A few challenges with using these regulatory methods to estimate a WDI using published data from studies where drugs are administered ELDU include a lack of established TOLs or MRLs, sampling times focusing on therapeutic drug use rather than drug depletion, breed variation, animal subject numbers that fulfill metabolism vs drug residue focused studies, and uneven distribution of sexes and ages of the study animals Because these regulatory methods use confidence interval approaches for estimating WDIs, they represent potential ranges of the population mean vs the sample mean and could provide a more conservative ELDU WDI estimate, as required by the Animal Medicinal Drug Use Clarification Act (AMDUCA)

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Conclusion