Pharmacokinetics of oral and subcutaneous meloxicam: Effect on indicators of pain and inflammation after knife castration in weaned beef calves
Meléndez, D.M., Marti, S., Pajor, E.A., Sidhu, P.K., Gellatly, D., Janzen, E.D., Schwinghamer, T.D., Coetzee, J.F., Schwartzkopf-Genswein, K.S. (2019). Pharmacokinetics of oral and subcutaneous meloxicam: Effect on indicators of pain and inflammation after knife castration in weaned beef calves. PLoS ONE, [online] 14(5), http://dx.doi.org/10.1371/journal.pone.0217518
Plain language summary
Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase-2 (COX-2) enzymes which convert arachidonic acid into pro-inflammatory prostaglandins. Meloxicam is approved for its use in cattle in the European Union and Canada, and it is an attractive analgesic option as it is effective following a single dose administration due to its long half-life in calves (subcutaneous (SC) = 16.4 h; oral (PO) = 27.5 h). In Canada, meloxicam is available for use in cattle in two presentations: meloxicam oral (PO) suspension (1.0 mg/kg) labelled for reducing pain and inflammation associated with band and knife castration and, injectable meloxicam (0.5 mg/kg) labelled as an adjuvant for diarrhea, mastitis, de-budding and abdominal surgery.
The Canadian Beef Codes of Practice has set as a requirement the use of pain mitigation when performing painful husbandry procedures such as castration, spaying and dehorning. Castration is a routine practice which improves cattle management, avoids unwanted reproduction and increases meat quality. The aim of this study was to compare the pharmacokinetics (PK) of SC and PO meloxicam and to assess the effect of different routes of meloxicam administration on indicators of pain and inflammation in 7–8 month old calves during and after knife castration. We hypothesize that indicators of pain and inflammation will be mitigated after PO and SC administration but the effect will be observed at different time points after castration due to differences in PK.
Oral meloxicam is labelled for reducing pain and inflammation associated with castration in cattle in Canada, however, subcutaneous meloxicam is only labelled for pain associated with dis-budding and abdominal surgery. The aim of this project was to determine the pharmacokinetic profile of oral (PO; 1.0 mg/kg BW) and subcutaneous meloxicam (SC; 0.5 mg/ kg BW), and to assess the effect of meloxicam on physiological and behavioural indicators of pain associated with knife castration in 7–8 month old calves. Twenty-three Angus crossbred beef calves (328 ± 4.4 kg BW) were randomly assigned to two treatments: PO n = 12 or SC n = 11 administration of meloxicam immediately before knife castration. Physiological parameters included salivary and hair cortisol, substance P, haptoglobin, serum amyloid-A, weight, complete blood count, scrotal and rectal temperature. Behavioural parameters included standing and lying behaviour, pen behaviour and feeding behaviour. Data were analyzed using PROC GLIMMIX (SAS), with repeated measures using mixed procedures including treatment as a fixed effect and animal and pen as a random effect. The pharmacokinetic profile of the drug including area under the curve, volume of distribution and clearance was greater (P < 0.05) in PO than SC calves. After surgery, substance P concentrations, white blood cell counts (WBC), weight and lying duration were greater (P < 0.05) in PO than SC calves, while scrotal circumference was lower (P < 0.05) in PO calves than SC calves. Although statistical differences were observed for pharmacokinetic, physiological and behavioural parameters differences were small and may lack biological relevance.