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Effects of SLCO1B1 and SLCO1B3 Genetic Polymorphisms on Valsartan Pharmacokinetics in Healthy Korean Volunteers

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dc.contributor.author박경수-
dc.date.accessioned2022-05-09T16:50:19Z-
dc.date.available2022-05-09T16:50:19Z-
dc.date.issued2021-09-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/188231-
dc.description.abstractPurpose: This study aimed to examine OATP1B1 (SLCO1B1) and OATP1B3 (SLCO1B3) on the pharmacokinetics of valsartan. Twenty-five subjects were genotyped for 16 single-nucleotide polymorphisms of the SLCO1B1 and SLCO1B3 genes. Methods: After a single dose of 160 mg of valsartan was orally administered to healthy male volunteers, drug concentrations were assayed up to 48 h. The 25 subjects were genotyped for 16 single-nucleotide polymorphisms (SNPs) of the SLCO1B1 and SLCO1B3 genes. Subjects were classified into groups according to their SLCO1B1*1B haplotype; 23 subjects were carriers of SLCO1B1*1B and two subjects were included in the reference group with SLCO1B1*1A/*1A. Alternations of the splicing factor-binding site pattern caused by the given mutation were evaluated with the Human Splicing Finder (HSF) 3.1. Results: The subjects who carried SLCO1B1*1B showed a 2.3-fold higher clearance than those without the *1B haplotype. Mean Cmax and AUCinf were reduced by 45% and 54%, respectively, in the SLCO1B1*1B genotype group compared to the reference group with the *1A/*1A genotype (p < 0.01). The carriers of the rs4149153 T allele of SLCO1B3 had a 27% lower mean Cmax and a 1.5-fold higher Vd compared to homozygotic CC carriers (p < 0.05). In a combined analysis of SLCO1B1 and SLCO1B3, subjects not carrying SLCO1B1 *1B and carrying SLCO1B3 rs4149153 T allele showed a 1.6-fold higher clearance than those with the other genotypes, whereas mean Cmax and AUClast were reduced by 35% and 42%, respectively (p < 0.05), in the subjects. HSF 3.1 analysis showed that rs4149153 could cause alterations of the acceptor splice site (TAAATACTAAAGAC to TAAATATTAAAGAC) with scoring change (from 72.57 to 71.92, difference = -0.9). Conclusion: It was found that plasma exposure to valsartan is significantly decreased in SLCO1B1*1B carriers and carriers of the rs4149153 T allele of SLCO1B3, possibly as a result of increased hepatic uptake.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherMDPI-
dc.relation.isPartOfJOURNAL OF PERSONALIZED MEDICINE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleEffects of SLCO1B1 and SLCO1B3 Genetic Polymorphisms on Valsartan Pharmacokinetics in Healthy Korean Volunteers-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pharmacology (약리학교실)-
dc.contributor.googleauthorGonjin Song-
dc.contributor.googleauthorJee-Eun Chung-
dc.contributor.googleauthorJeong Yee-
dc.contributor.googleauthorKyung-Eun Lee-
dc.contributor.googleauthorKyungsoo Park-
dc.contributor.googleauthorHye-Sun Gwak-
dc.identifier.doi10.3390/jpm11090862-
dc.contributor.localIdA01422-
dc.relation.journalcodeJ04078-
dc.identifier.eissn2075-4426-
dc.identifier.pmid34575639-
dc.subject.keywordSLCO1B1-
dc.subject.keywordSLCO1B3-
dc.subject.keywordSingle nucleotide polymorphism-
dc.subject.keywordpharmacokinetics-
dc.subject.keywordvalsartan-
dc.contributor.alternativeNamePark, Kyung Soo-
dc.contributor.affiliatedAuthor박경수-
dc.citation.volume11-
dc.citation.number9-
dc.citation.startPage862-
dc.identifier.bibliographicCitationJOURNAL OF PERSONALIZED MEDICINE, Vol.11(9) : 862, 2021-09-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

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