Comparative population pharmacokinetics and absolute oral bioavailability of COX-2 selective inhibitors celecoxib, mavacoxib and meloxicam in cockatiels (Nymphicus hollandicus)

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... Mehr ...

Verfasser: Dhondt, Laura
Devreese, Mathias
Croubels, Siska
De Baere, Siegrid
Haesendonck, Roel
Goessens, Tess
Gehring, Ronette
De Backer, Patrick
Antonissen, Gunther
Dokumenttyp: Artikel
Erscheinungsdatum: 2017
Reihe/Periodikum: Scientific Reports ; volume 7, issue 1 ; ISSN 2045-2322
Verlag/Hrsg.: Springer Science and Business Media LLC
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29093244
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : http://dx.doi.org/10.1038/s41598-017-12159-z

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 (T 1/2el = 0.88 h) and meloxicam (T 1/2el = 0.90 h), mavacoxib has a prolonged elimination half-life (T 1/2el = 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.