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

Autor: Jiayang He, Ping Fang, Jian Wen, Teng-Hui Liu, Bowen Zhang, Xiang Zheng, Chen-Chen Wang, Ren-ai Xu
Rok vydání: 2018
Předmět:
CYP2C9
musculoskeletal diseases
0301 basic medicine
Male
Letter
Pharmaceutical Science
Administration
Oral
Pharmacology
In Vitro Techniques
Rats
Sprague-Dawley
03 medical and health sciences
Structure-Activity Relationship
0302 clinical medicine
Pharmacokinetics
Cytochrome P-450 CYP1A2
In vivo
Drug Discovery
Acetamides
medicine
Agomelatine
Animals
Humans
heterocyclic compounds
skin and connective tissue diseases
Incubation
Original Research
Cytochrome P-450 CYP2C9
Drug Design
Development and Therapy
Dose-Response Relationship
Drug
Molecular Structure
Chemistry
organic chemicals
Metabolism
In vitro
Recombinant Proteins
Rats
030104 developmental biology
Celecoxib
Microsomes
Liver
lipids (amino acids
peptides
and proteins)
agomelatine
pharmacokinetics
liver microsomes
030217 neurology & neurosurgery
medicine.drug
Zdroj: Drug Design, Development and Therapy
ISSN: 1177-8881
Popis: Jiayang He,1 Ping Fang,2 Xiang Zheng,2 Chenchen Wang,2 Tenghui Liu,2 Bowen Zhang,2 Jian Wen,2 Ren-ai Xu3 1Department of Pharmacy, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China; 2Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, Zhejiang, China; 3Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China 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
Databáze: OpenAIRE
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