The plasma concentrations and pharmacokinetics of two novel methods of meloxicam delivery for sustained and practical pain mitigation in dairy calves
Year: 2020
Chloe Wilson
University of Sydney, Australia
Supervisor(s): Dr Sabrina Lomax and Dr Dominique Van der Saag
The non-steroidal anti-inflammatory drug (NSAID) meloxicam is commonly administered to livestock to alleviate the pain associated with surgical husbandry procedures. Pain inflicted by these procedures often persists beyond the duration of action offered by commercial NSAIDS, and therefore novel forms of administration to extend duration of action are required. This study aimed to investigate two novel forms of meloxicam delivery, a sustained release meloxicam formulation (SR-M) and a meloxicam medicated pellet (MMP), in order to achieve sustained action, aligning with the long-term pain of operative procedures. In the first experiment, three Holstein Friesian calves (avg 171.1kg ± 14.7 SD in Phase 1, 194.7kg ± 17 SD in Phase 2) were administered a SR-M formulation at 1.0mg/kg subcutaneously. Blood samples were collected at 0h, 2h, 4h, 6h, 8h, 10h, 12h, 24h and days 2, 4, 5, 6, 7, 10, 14, relative to administration. In experiment two, twelve Holstein Friesian calves (avg 85 kg ± 18.7 kg SD) were offered a MMP feed, dosed with meloxicam at 1mg/kg of bodyweight. Blood samples were collected at 0h and daily for 9 days. Plasma meloxicam concentrations was determined by HPLC analysis with UV detection. Within Phase 1 and Phase 2, respectively, the SR-M formulation displayed an average t1/2 of 25.43 hrs (±5.00 h) and 55.54 h (±3.15 h) and a mean Cmax of 0.61 ug/mL (±0.21 ug/mL) and 0.76 ug/mL (±0.12 ug/mL), occurring at an average Tmax of 3.33 h (±1.15 h) and 10.67 h (±2.31 h). The MMP feed exhibited maximum plasma levels of 3.81ug/mL (± 1.05 ug/mL), on Day 1, which increased daily until highest concentrations on Day 6 at 6.95 ug/mL (± 2.17 ug/mL).The MMP formulation displayed an elimination t1/2 of 15.97 h (±6.09 h) and elimination rate (kel) 0.04 h-1 (±0.01 h-1). Although both forms of meloxicam delivery demonstrated variable findings, these novel mitigation options indicate the potential to extend duration of action of meloxicam, however additional research is required to determine clinical efficacy.