Variability of the drug response to nonsteroidal anti-inflammatory drugs according to cyclooxygenase-2 genetic polymorphism
- Authors
- Lee, Sook Joung; Park, Min Kyu; Shin, Dong-Seong; Chun, Min Ho
- Issue Date
- 2017
- Publisher
- DOVE MEDICAL PRESS LTD
- Keywords
- nonsteroidal anti-inflammatory agent; cyclooxygenase-2; single-nucleotide polymorphism; drug response; pharmacodynamics; clinical trial
- Citation
- DRUG DESIGN DEVELOPMENT AND THERAPY, v.11, pp.2727 - 2736
- Journal Title
- DRUG DESIGN DEVELOPMENT AND THERAPY
- Volume
- 11
- Start Page
- 2727
- End Page
- 2736
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/7487
- DOI
- 10.2147/DDDT.S143807
- ISSN
- 1177-8881
- Abstract
- Purpose: Cyclooxygenase (COX) is the main pharmacodynamic target of nonsteroidal anti-inflammatory drugs (NSAIDs). We investigated the inhibitory effects on COX-2 after NSAIDs administration using a lipopolysaccharide (LPS)-derived COX-2 induction model in whole blood, according to the genotypes of COX-2 single-nucleotide polymorphisms (SNPs). Patients and methods: Seven genotypes of COX-2 SNPs were selected from public databases and analyzed in 324 healthy subjects. Two genotypes showing a high percentage of variability were selected. A clinical trial examining pharmacodynamics according to the genotype of two SNPs (rs5275 and rs689466) was conducted. Twenty subjects were administered a single oral dose of 200 mg of celecoxib, and pharmacokinetic and pharmacodynamic analyses were performed. Results: In the analysis of the pharmacokinetic parameters, significant differences in drug exposure were not investigated for each SNP genotype. The pharmacodynamic analysis revealed that the maximum effect of COX-2 inhibition was achieved at 2.0 hours for all genotypes of COX-2 SNPs after a single oral administration of 200 mg celecoxib. The inhibitory effects according to the genotype of COX-2 SNPs were investigated, and the area under the effect curve of the rs689466 GG genotype was significantly lower than that for the AA or AG genotype. Conclusion: Our results demonstrated that inhibitory effects of celecoxib on COX-2 induction were different according to the genotype of COX-2 SNPs. In the present study, rs689466 is responsible for the variability of the response to celecoxib, suggesting that a subject with the GG genotype of rs689466 would be more responsive to celecoxib in terms of COX-2 inhibition.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 의과대학 > 의예과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/7487)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.