Variability of the drug response to nonsteroidal anti-inflammatory drugs according to cyclooxygenase-2 genetic polymorphism
DC Field | Value | Language |
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dc.contributor.author | Lee, Sook Joung | - |
dc.contributor.author | Park, Min Kyu | - |
dc.contributor.author | Shin, Dong-Seong | - |
dc.contributor.author | Chun, Min Ho | - |
dc.date.available | 2020-02-27T23:41:47Z | - |
dc.date.created | 2020-02-07 | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 1177-8881 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/7487 | - |
dc.description.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. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | DOVE MEDICAL PRESS LTD | - |
dc.relation.isPartOf | DRUG DESIGN DEVELOPMENT AND THERAPY | - |
dc.subject | RISK | - |
dc.subject | BREAST | - |
dc.subject | ASSOCIATION | - |
dc.subject | PROSTATE | - |
dc.subject | CANCERS | - |
dc.subject | BIOLOGY | - |
dc.subject | PTGS2 | - |
dc.title | Variability of the drug response to nonsteroidal anti-inflammatory drugs according to cyclooxygenase-2 genetic polymorphism | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000410501200003 | - |
dc.identifier.doi | 10.2147/DDDT.S143807 | - |
dc.identifier.bibliographicCitation | DRUG DESIGN DEVELOPMENT AND THERAPY, v.11, pp.2727 - 2736 | - |
dc.identifier.scopusid | 2-s2.0-85029726306 | - |
dc.citation.endPage | 2736 | - |
dc.citation.startPage | 2727 | - |
dc.citation.title | DRUG DESIGN DEVELOPMENT AND THERAPY | - |
dc.citation.volume | 11 | - |
dc.contributor.affiliatedAuthor | Shin, Dong-Seong | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | nonsteroidal anti-inflammatory agent | - |
dc.subject.keywordAuthor | cyclooxygenase-2 | - |
dc.subject.keywordAuthor | single-nucleotide polymorphism | - |
dc.subject.keywordAuthor | drug response | - |
dc.subject.keywordAuthor | pharmacodynamics | - |
dc.subject.keywordAuthor | clinical trial | - |
dc.subject.keywordPlus | RISK | - |
dc.subject.keywordPlus | BREAST | - |
dc.subject.keywordPlus | ASSOCIATION | - |
dc.subject.keywordPlus | PROSTATE | - |
dc.subject.keywordPlus | CANCERS | - |
dc.subject.keywordPlus | BIOLOGY | - |
dc.subject.keywordPlus | PTGS2 | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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