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Effects of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of atorvastatin and 2-hydroxyatorvastatin in healthy Korean subjects
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 이민구 | - |
dc.contributor.author | 이윤정 | - |
dc.contributor.author | 임아영 | - |
dc.contributor.author | 장성복 | - |
dc.contributor.author | 정재용 | - |
dc.date.accessioned | 2015-04-23T16:22:04Z | - |
dc.date.available | 2015-04-23T16:22:04Z | - |
dc.date.issued | 2010 | - |
dc.identifier.issn | 0946-1965 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/100454 | - |
dc.description.abstract | OBJECTIVE: This study aimed to evaluate the effect of genetic polymorphisms of SLCO1B1 and ABCB1 on the pharmacokinetics of atorvastatin and its metabolites. METHODS: 290 Koreans were genotyped for SLCO1B1, ABCB1 and CYP3A5, and 28 subjects were selected for the pharmacokinetic study. Each subject received a single oral dose of 20 mg atorvastatin and blood samples were collected up to 48 hr after dosing. The relationship between the genotypes and atorvastatin pharmacokinetics was examined. RESULTS: For SLCO1B1 genotypes, the mean area under the concentration-time curve from time 0 to infinity (AUC0-infinity) of atorvastatin was 148.2 ng x hr/ml for *15/*15 subjects (n = 3), which was significantly larger than for 1a/*15 and *1b/*15 (n = 8) (80.7 ng x hr/ml, p = 0.0121) and also larger than for *1a/*1a, *1a/*1b and *1b/*1b (n = 17) (66.3 ng x hr/ml, p = 0.0018). The mean AUC0-infinity of 2-hydroxyatorvastatin for *15/*15 was also larger than in *1a/*1a, *1a/*1b and *1b/*1b (p = 0.012). In lactone forms, no significant pharmacokinetic difference was found among the genotypes. For ABCB1 genotypes, the half-lives of atorvastatin, atorvastatin lactone, 2-hydroxyatorvastatin and 2-hydroxyatorvastatin lactone were significantly longer in c.2677TT-c.3435TT (n = 3) vs. c.2677GG-c.3435CC and c.2677GT-c.3435CT (n = 10), yielding p = 0.049, 0.007, 0.007 and 0.007, respectively. CONCLUSION: This study shows that the SLCO1B1*15 allele may be associated with the individual difference in the AUC0-infinity of atorvastatin whereas the ABCB1 TT-TT diplotype may affect the elimination half-life of the drug in the Korean population. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 36~45 | - |
dc.relation.isPartOf | INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | ATP Binding Cassette Transporter, Sub-Family B | - |
dc.subject.MESH | ATP-Binding Cassette, Sub-Family B, Member 1/genetics* | - |
dc.subject.MESH | Adult | - |
dc.subject.MESH | Alleles | - |
dc.subject.MESH | Area Under Curve | - |
dc.subject.MESH | Asian Continental Ancestry Group | - |
dc.subject.MESH | AtorvastatinCalcium | - |
dc.subject.MESH | Cytochrome P-450 CYP3A/genetics | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Genotype | - |
dc.subject.MESH | Half-Life | - |
dc.subject.MESH | Heptanoic Acids/pharmacokinetics* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacokinetics* | - |
dc.subject.MESH | Korea | - |
dc.subject.MESH | Lactones/pharmacokinetics | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Organic Anion Transporters/genetics* | - |
dc.subject.MESH | Pyrroles/pharmacokinetics* | - |
dc.subject.MESH | Solute Carrier Organic Anion Transporter Family Member 1b1 | - |
dc.subject.MESH | Young Adult | - |
dc.title | Effects of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of atorvastatin and 2-hydroxyatorvastatin in healthy Korean subjects | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pharmacology (약리학) | - |
dc.contributor.googleauthor | 박영아 | - |
dc.contributor.googleauthor | 김정은 | - |
dc.contributor.googleauthor | 남궁란 | - |
dc.contributor.googleauthor | 박민수 | - |
dc.contributor.googleauthor | 박국인 | - |
dc.contributor.googleauthor | 이철 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A02781 | - |
dc.contributor.localId | A03023 | - |
dc.contributor.localId | A03383 | - |
dc.contributor.localId | A03436 | - |
dc.contributor.localId | A03709 | - |
dc.relation.journalcode | J01098 | - |
dc.identifier.pmid | 20040338 | - |
dc.identifier.url | http://www.dustri.com/nc/journals-in-english/mag/int-journal-of-clinical-pharmacology-and-therapeutics/vol/volume-48/issue/january-18.html | - |
dc.subject.keyword | SLCO1B1 | - |
dc.subject.keyword | ABCB1 | - |
dc.subject.keyword | polymorphism | - |
dc.subject.keyword | atorvastatin | - |
dc.subject.keyword | pharmacokinetics | - |
dc.contributor.alternativeName | Lee, Min Goo | - |
dc.contributor.alternativeName | Lee, Yoon Jung | - |
dc.contributor.alternativeName | Lim, Lay Ahyoung | - |
dc.contributor.alternativeName | Jang, Seong Bok | - |
dc.contributor.alternativeName | Chung, Jae Yong | - |
dc.contributor.affiliatedAuthor | Lee, Min Goo | - |
dc.contributor.affiliatedAuthor | Lee, Yoon Jung | - |
dc.contributor.affiliatedAuthor | Lim, Lay Ahyoung | - |
dc.contributor.affiliatedAuthor | Jang, Seong Bok | - |
dc.contributor.affiliatedAuthor | Chung, Jae Yong | - |
dc.citation.volume | 48 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 36 | - |
dc.citation.endPage | 45 | - |
dc.identifier.bibliographicCitation | INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS, Vol.48(1) : 36-45, 2010 | - |
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