Inhibitory effect of celecoxib on agomelatine metabolism in vitro and in vivo

• Published in: Drug design, development and therapy development and therapy, 2018-01, Vol.12, p.513-519
• Main Authors: He, Jiayang, Fang, Ping, Zheng, Xiang, Wang, Chenchen, Liu, Tenghui, Zhang, Bowen, Wen, Jian, Xu, Ren-Ai
• Format: Article
• Language: English
• Subjects: Acetamides - administration & dosage; Acetamides - metabolism; Administration, Oral; Agomelatine; Animals; Anti-inflammatory agents; Anxiety; Arthritis; Celecoxib; Celecoxib - administration & dosage; Celecoxib - pharmacology; CYP2C9; Cytochrome; Cytochrome P-450; Cytochrome P-450 CYP2C9 - metabolism; Dose-Response Relationship, Drug; Humans; In vitro methods and tests; In Vitro Techniques; In vivo methods and tests; Incubation; Inflammation; Liver; liver microsomes; Male; Melatonin; Metabolism; Metabolites; Microsomes; Microsomes, Liver - drug effects; Microsomes, Liver - metabolism; Molecular Structure; Nonsteroidal anti-inflammatory agents; Original Research; Pharmacokinetics; Pharmacy; Physiological aspects; Rats; Rats, Sprague-Dawley; Recombinant Proteins - metabolism; Structure-Activity Relationship
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S160316

The aim of this study was to study the effect of celecoxib on agomelatine metabolism in vitro and in vivo. 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. 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. Thus, more attention should be paid when celecoxib is administered combined with agomelatine.