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Authors He JY, Fang P, Zheng X, Wang CC, Liu TH, Zhang BW, Wen J, Xu RA
Received 19 December 2017
Accepted for publication 31 January 2018
Published 9 March 2018 Volume 2018:12 Pages 513—519
DOI https://doi.org/10.2147/DDDT.S160316
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Palas Chanda
Peer reviewer comments 3
Editor who approved publication: Dr Anastasios Lymperopoulos
Aim: The aim of this study was to
study the effect of celecoxib on agomelatine metabolism in vitro and in
vivo.
Methods: Ten
healthy male Sprague–Dawley rats were randomly divided into 2 groups: Group A
(control group) and Group B (30 mg/kg celecoxib). Then a single dose of 20
mg/kg agomelatine was administered orally 30 min after administration of
celecoxib. In an in vitro study, celecoxib with a series of concentrations was
added to an incubation mixture containing recombinant human CYP2C9, human or
rat liver microsomes to determine the half-maximal inhibitory concentration on
the metabolism of agomelatine. Moreover, a mechanism study was performed to
determine the inhibitory effect of celecoxib on CYP2C9.
Results: The
results showed that a single dose of 30 mg/kg celecoxib significantly increased
the area under the concentration-time curve and maximum concentration of
agomelatine. In addition, celecoxib inhibited the metabolism of agomelatine in
the in vitro studies, which was determined to be by a competitive mechanism on
CYP2C9. Those results indicated that celecoxib has an inhibitory effect on the
metabolism of agomelatine both in vivo and in vitro.
Conclusion: Thus,
more attention should be paid when celecoxib is administered combined with
agomelatine.
Keywords: agomelatine,
liver microsomes, pharmacokinetics, celecoxib, CYP2C9