Influence of ABCB1 and CYP3A5 genetic polymorphisms on the pharmacokinetics of quetiapine in healthy volunteers
DC Field | Value | Language |
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dc.contributor.author | Kim, Kyoung-Ah | - |
dc.contributor.author | Joo, Hyun-Jin | - |
dc.contributor.author | Lee, Hae-Mi | - |
dc.contributor.author | Park, Ji-Young | - |
dc.date.accessioned | 2021-09-05T12:57:53Z | - |
dc.date.available | 2021-09-05T12:57:53Z | - |
dc.date.created | 2021-06-15 | - |
dc.date.issued | 2014-01 | - |
dc.identifier.issn | 1744-6872 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/99746 | - |
dc.description.abstract | Background and objectivesQuetiapine is an atypical antipsychotic drug used to treat schizophrenia and acute episodes of mania. Quetiapine is metabolized by CYP3A enzymes including CYP3A5 and is a substrate of P-glycoprotein, an efflux drug transporter encoded by the ABCB1 gene. We assessed the effects of ABCB1 [c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), c.3435C>T (rs1045642)] and CYP3A5*3 (6986A>G) (rs776746) polymorphisms on the pharmacokinetics of quetiapine in humans.Materials and methodsForty healthy male individuals were enrolled, and their ABCB1 and CYP3A5 polymorphisms were assessed. After a single dose of 100 mg quetiapine was administered, plasma concentrations of quetiapine were measured for 24 h and pharmacokinetic analysis was carried out.ResultsThe ABCB1 polymorphisms including c.1236C>T, c.2677G>T/A, and c.3435C>>T did not affect plasma levels of quetiapine, and its pharmacokinetic parameters did not differ among ABCB1 genotype groups. However, the CYP3A5*3 polymorphism significantly affected the plasma level of quetiapine and its pharmacokinetics. The peak plasma concentration of quetiapine was 208.39 ng/ml for CYP3A5*1/*1, 243.46 ng/ml for CYP3A5*1/*3, and 332.94 ng/ml for CYP3A5*3/*3 (P=0.0118). The mean AUC(inf) (area under the time vs. concentration curve from 0 to infinity) value was 627.3, 712.77, and 1045.29 ng h/ml, respectively (P=0.0017).ConclusionThe results indicated that the genetic polymorphism of CYP3A5*3 but not ABCB1 significantly influences the plasma level of quetiapine and its pharmacokinetics. These findings suggest that the CYP3A5 genetic polymorphism affects the disposition of quetiapine and provide a plausible explanation for interindividual variation in the disposition of this drug. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | LIPPINCOTT WILLIAMS & WILKINS | - |
dc.subject | EXTENDED-RELEASE QUETIAPINE | - |
dc.subject | TRANSPORTER P-GLYCOPROTEIN | - |
dc.subject | BIPOLAR-II DEPRESSION | - |
dc.subject | DOUBLE-BLIND | - |
dc.subject | CYP3A5-ASTERISK-3 GENOTYPE | - |
dc.subject | N-DESALKYLQUETIAPINE | - |
dc.subject | KOREAN SUBJECTS | - |
dc.subject | BRAIN ENTRY | - |
dc.subject | IN-VIVO | - |
dc.subject | EXPRESSION | - |
dc.title | Influence of ABCB1 and CYP3A5 genetic polymorphisms on the pharmacokinetics of quetiapine in healthy volunteers | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Kyoung-Ah | - |
dc.contributor.affiliatedAuthor | Park, Ji-Young | - |
dc.identifier.doi | 10.1097/FPC.0000000000000020 | - |
dc.identifier.scopusid | 2-s2.0-84891025545 | - |
dc.identifier.wosid | 000328629800005 | - |
dc.identifier.bibliographicCitation | PHARMACOGENETICS AND GENOMICS, v.24, no.1, pp.35 - 42 | - |
dc.relation.isPartOf | PHARMACOGENETICS AND GENOMICS | - |
dc.citation.title | PHARMACOGENETICS AND GENOMICS | - |
dc.citation.volume | 24 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 35 | - |
dc.citation.endPage | 42 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biotechnology & Applied Microbiology | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Biotechnology & Applied Microbiology | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | EXTENDED-RELEASE QUETIAPINE | - |
dc.subject.keywordPlus | TRANSPORTER P-GLYCOPROTEIN | - |
dc.subject.keywordPlus | BIPOLAR-II DEPRESSION | - |
dc.subject.keywordPlus | DOUBLE-BLIND | - |
dc.subject.keywordPlus | CYP3A5-ASTERISK-3 GENOTYPE | - |
dc.subject.keywordPlus | N-DESALKYLQUETIAPINE | - |
dc.subject.keywordPlus | KOREAN SUBJECTS | - |
dc.subject.keywordPlus | BRAIN ENTRY | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordAuthor | ABCB1 | - |
dc.subject.keywordAuthor | CYP3A5 | - |
dc.subject.keywordAuthor | P-glycoprotein | - |
dc.subject.keywordAuthor | pharmacokinetics | - |
dc.subject.keywordAuthor | quetiapine | - |
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