Cited 5 times in
Effects of SLCO1B1 and SLCO1B3 Genetic Polymorphisms on Valsartan Pharmacokinetics in Healthy Korean Volunteers
DC Field | Value | Language |
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dc.contributor.author | 박경수 | - |
dc.date.accessioned | 2022-05-09T16:50:19Z | - |
dc.date.available | 2022-05-09T16:50:19Z | - |
dc.date.issued | 2021-09 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/188231 | - |
dc.description.abstract | Purpose: 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.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | MDPI | - |
dc.relation.isPartOf | JOURNAL OF PERSONALIZED MEDICINE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | Effects of SLCO1B1 and SLCO1B3 Genetic Polymorphisms on Valsartan Pharmacokinetics in Healthy Korean Volunteers | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pharmacology (약리학교실) | - |
dc.contributor.googleauthor | Gonjin Song | - |
dc.contributor.googleauthor | Jee-Eun Chung | - |
dc.contributor.googleauthor | Jeong Yee | - |
dc.contributor.googleauthor | Kyung-Eun Lee | - |
dc.contributor.googleauthor | Kyungsoo Park | - |
dc.contributor.googleauthor | Hye-Sun Gwak | - |
dc.identifier.doi | 10.3390/jpm11090862 | - |
dc.contributor.localId | A01422 | - |
dc.relation.journalcode | J04078 | - |
dc.identifier.eissn | 2075-4426 | - |
dc.identifier.pmid | 34575639 | - |
dc.subject.keyword | SLCO1B1 | - |
dc.subject.keyword | SLCO1B3 | - |
dc.subject.keyword | Single nucleotide polymorphism | - |
dc.subject.keyword | pharmacokinetics | - |
dc.subject.keyword | valsartan | - |
dc.contributor.alternativeName | Park, Kyung Soo | - |
dc.contributor.affiliatedAuthor | 박경수 | - |
dc.citation.volume | 11 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 862 | - |
dc.identifier.bibliographicCitation | JOURNAL OF PERSONALIZED MEDICINE, Vol.11(9) : 862, 2021-09 | - |
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