Comparative Pharmacokinetics of Meloxicam Between Healthy Post-partum vs. Mid-lactation Dairy Cattle

Abstract

Lactating dairy cattle are at risk for various painful conditions throughout their life, such as lameness, parturition, mastitis, and metabolic disorders. These conditions necessitate adequate methods of analgesia to address welfare concerns through efficacious pain mitigation. As no method of analgesia has been approved for lactating dairy cattle, to date, research is necessary to determine effective pain management strategies for dairy cattle. In both the European Union and Canada, meloxicam has been approved for use in lactating dairy cattle as a methodology for pain control. The objective of this study was to characterize the pharmacokinetics of meloxicam administered orally and intravenously to lactating dairy cattle in the post-partum vs. mid-lactation period. In this parallel study design, 12 healthy, lactating Holsteins were enrolled within 24 h of freshening and randomly allocated to intravenous (0.2 mg/kg) or oral (1.0 mg/kg) meloxicam administration treatment groups. They were matched based on parity to 12, healthy cows that were considered mid-lactation [>150 days-in-milk (DIM)] to receive the same treatment. Based on meloxicam formulation, sampling times varied and plasma was collection via jugular venipuncture for 6 days. Plasma drug concentrations were evaluated using liquid chromatography coupled with mass spectroscopy and pharmacokinetic properties were evaluated using non-compartmental (i.e., statistical moments) analysis. Results indicated a decreased systemic clearance of meloxicam in post-partum relative to mid-lactation cows, which resulted in a longer half-life and increased total exposure independent of mode of administration. These results suggest a need for dose adjustments based on stage in lactation and further assessment of the impact of days-in-milk on milk withholding period.

Pharmacokinetics, Milk Residues, and Toxicological Evaluation of a Single High Dose of Meloxicam Administered at 30 mg/kg per os to Lactating Dairy Cattle

“…This also suggests that excretion is not impacted by the increased dose. Oral clearance was also similar to cattle studies using a 1 mg/kg PO dosing regimen [19,22]. Plasma concentrations following 30 mg/kg meloxicam administrations at 120th hour were similar to the Cmax reported in 1 mg/kg dose studies in cattle.…”

“…The C max in the present study was similar to sows dosed with the same dose (30 mg/kg meloxicam PO) approaching 100 ug/mL [18]. Plasma C max was approximately 30 times higher than the reported C max for studies using 1 mg/kg dose in cattle that reported plasma C max ranging from 1.45-3.10 µg/mL [19][20][21][22][23]. The much higher C max and longer T max were likely directly due to the delivered dose being 30 times higher.…”

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

“…The AUC 0-inf generally appears to be greater for cattle [14,15,[19][20][21][32][33][34][35][36] than for the sheep in our study, which suggests greater drug exposure in cattle compared to sheep in this study. Coetzee et al [15] Wani et al [37] Allen et al [14] Allen et al [14] Gorden et al [21] Gorden et al [21] Shock et al [36] Warner et al [38] Warner et al [38] Publication…”