Plasma pharmacokinetics, milk residue depletion profile, and milk withdrawal interval estimation following multiple dose oral administration of meloxicam to lactating dairy goats

Melissa A Mercer¹Zhicheng Zhang²Maaike Clapham¹Scott E Wetzlich¹Fauna Leah Smith³Benjamin Rupchis⁴Zhoumeng Lin^2*Lisa Ann Tell^1*

• ¹Department of Veterinary Medicine and Epidemiology, University of California, Davis, Davis, United States
• ²Department of Environmental and Global Health, University of Florida, Gainesville, United States
• ³Department of Population Health and Reproduction, University of California, Davis, Davis, United States
• ⁴Department of Animal Science, University of California, Davis, Davis, United States

Meloxicam is frequently administered orally to lactating dairy goats in an extra-label manner, but since FDA approved withdrawal times have not been established and raises concerns for potential drug residues in milk. This study aimed to estimate plasma pharmacokinetics, determine meloxicam residues in milk based on concentration versus time depletion profiles and calculate estimated withdrawal interval (WDI) recommendations for meloxicam following multiple oral doses administered to lactating dairy goats.Meloxicam was administered to healthy mid-lactation dairy goats (n=10) at 1 mg/kg orally every 24 hr for a total of 6 doses. Meloxicam was quantified in plasma and milk samples using high performance liquid chromatography with an ultraviolet detector. Plasma pharmacokinetic parameters were estimated using a non-compartmental approach and theoretical milk elimination half-life was estimated. Milk WDIs were calculated using the FDA tolerance limit method under different data simulation scenarios and compared to the standard FDA regulatory approach of 10 animals with triplicate samples. Additional assessment included the EMA maximum residue limit (MRL) method and the theoretical terminal elimination half-life method.Following the final administered dose, the geometric mean plasma estimated plasma T1/2 of 7.64 hr (range 5.61-9.47 hr), while the geometric mean milk theoretical estimated T1/2 was 6.96 hr (range 5.47-9.56 hr). WDI estimations using the FDA tolerance limit method targeting the analytical limit of detection (4 ng/mL) ranged from 70.1 to 82.8 hr, and the WDI estimated using the EMA MRL method targeting the EMA MRL (15 ng/mL) was 64.97 hr. Monte Carlo simulation of single replicate data closely approximated WDI estimates from full triplicate datasets, whereas simulating additional virtual animals introduced relatively greater variability in the estimated WDI.This study estimated plasma pharmacokinetic parameters and theoretical milk residue depletion profiles for meloxicam following multiple oral doses administered to healthy lactating dairy goats. The theoretical elimination half-life of meloxicam for milk is shorter for goats than cattle, resulting in shorter estimated WDIs for the same dosing regimen. From a food safety perspective, meloxicam cattle WDTs or estimated WDIs may be appropriately conservative for application to goats when properly adjusted for dose, route, and regulatory tolerances/MRLs.