Abstract
Selective COX-2 inhibitors are non-steroidal anti-inflammatory drugs which directly target cyclooxygenase-2 (COX-2), an enzyme mainly responsible for induction of inflammation, pyresis and pain. Although commonly used in avian medicine, limited pharmacokinetic (PK) data in domestic and companion birds are available. In this study, PK parameters and absolute oral bioavailability expressed as percentage (F%) of celecoxib (10 mg/kg BW), mavacoxib (4 mg/kg BW) and meloxicam (1 mg/kg BW) were determined following single oral (PO) and intravenous (IV) administration to cockatiels (Nymphicus hollandicus). The drugs were quantified in plasma by liquid chromatography-tandem mass spectrometry. Data were processed using the nonlinear mixed effects (NLME) approach. In contrast to celecoxib (T1/2el = 0.88 h) and meloxicam (T1/2el = 0.90 h), mavacoxib has a prolonged elimination half-life (T1/2el = 135 h) following oral administration of a commercial formulation (CF). High to complete oral absorption was observed following oral administration of celecoxib (F% = 56–110%) and mavacoxib (F% = 111–113%), CF and standard solutions, respectively. In contrast, the F% of meloxicam was low (F% = 11%). Based on the presented results, a less frequent dosing of mavacoxib is proposed compared to celecoxib and meloxicam. However, pharmacodynamic and safety studies are necessary to further investigate the use of these NSAIDs in cockatiels.
Highlights
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in both veterinary and human medicine for their anti-inflammatory, analgesic and antipyretic properties
Inclusion of enterohepatic recirculation (EHR) in the model of meloxicam did not significantly improve the model fit (−2 log likelihood (−2LL), Akaike’s information criterion (AIC) and Bayesian information criterion (BIC)) (Table 4)
A comparative study was performed to evaluate the PK of three different COX 2 inhibitors, celecoxib, mavacoxib and meloxicam, in cockatiels (Nymphicus hollandicus) as a model for the order of Psittaciformes
Summary
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in both veterinary and human medicine for their anti-inflammatory, analgesic and antipyretic properties. Failure to appreciate the intensity of pain will confine the selection of an appropriate potent analgesic drug and corresponding dosing regimen[6] Both owners and clinicians must be familiar with the normal behaviour of both the animal species and the individual bird to recognize signs of pain[7,8]. Various NSAIDs, like meloxicam, piroxicam, carprofen, ketoprofen and celecoxib, have been used in birds to treat pain and inflammation, with meloxicam (Fig. 1a) as preferential COX-2 inhibitor being the most widely used in avian practice[8,13,14]. Allometric scaling showed poor correlations between BW and these PK parameters in different avian species[10] The coxibs, such as celecoxib and mavacoxib, have a highly specific action on the COX-2 enzyme. The PK properties and absolute oral bioavailability of celecoxib, mavacoxib and meloxicam in cockatiels (Nymphicus hollandicus) after single intravenous (IV) and oral (PO) administration using a popPK approach were assessed
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