Research Article: Pharmacokinetics of oral and subcutaneous meloxicam: Effect on indicators of pain and inflammation after knife castration in weaned beef calves

Date Published: May 24, 2019

Publisher: Public Library of Science

Author(s): Daniela M. Meléndez, Sonia Marti, Edmond A. Pajor, Pritam K. Sidhu, Désirée Gellatly, Eugene D. Janzen, Timothy D. Schwinghamer, Johann F. Coetzee, Karen S. Schwartzkopf-Genswein, Juan J. Loor.

http://doi.org/10.1371/journal.pone.0217518

Abstract

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.

Partial Text

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase-2 (COX-2) enzymes which convert arachidonic acid into pro-inflammatory prostaglandins [1]. 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) [2,3]. In Canada, meloxicam is available for use in cattle in two presentations: meloxicam 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.

This protocol was approved by the Animal Care Committee of Lethbridge Research and Development Centre (ACC number 1718). Animals were cared for in accordance with the Canadian Council of Animal Care guidelines [11].

The PK of meloxicam following intravenous (IV) or PO administration have been previously reported for cattle, sheep, goats, llamas and horses [3,27–32]. In the European Union and Canada, meloxicam has been approved for intramuscular (IM) and SC (0.5 mg/kg) use in cattle, as an adjunct therapy during the treatment of acute mastitis, diarrhea, respiratory disease and dehorning. In Canada PO meloxicam (1 mg/kg) has been approved for its use in cattle to mitigate pain associated with band and knife castration. The PK data are clinically useful as the terminal half-life of PO meloxicam at a dose of 1.0 mg/kg suggested that once a day administration provides analgesic efficacy in calves [3]. The PO route of drug administration is convenient, non-invasive, typically painless, and formulations are generally cheaper. Limitations of PO administration include a prolonged time of onset of analgesia after administration and unpredictable absorption due to varying gastric conditions and first pass hepatic biotransformation [33]. In contrast, SC administration offers the advantage of faster absorption and ease of administration. To our knowledge, there is only one previous study assessing PK following SC administration of meloxicam in cattle [2]. Therefore, the goals of this study were to describe the PK characteristics of meloxicam following SC administration to compare the pharmacokinetics of meloxicam after SC (0.5 mg/kg) and PO (1 mg/kg) administration. These data are important to optimize drug administration relative to the timing of the procedure and to design effective analgesic protocols for use in calves at the time of castration.

 

Source:

http://doi.org/10.1371/journal.pone.0217518

 

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