Effects of SLCO1B1 and SLCO1B3 Genetic Polymorphisms on Valsartan Pharmacokinetics in Healthy Korean Volunteers
- Title
- Effects of SLCO1B1 and SLCO1B3 Genetic Polymorphisms on Valsartan Pharmacokinetics in Healthy Korean Volunteers
- Author
- 정지은
- Keywords
- valsartan; SLCO1B1; SLCO1B3; Single nucleotide polymorphism; pharmacokinetics
- Issue Date
- 2021-08
- Publisher
- MDPI
- Citation
- JOURNAL OF PERSONALIZED MEDICINE, v. 11, NO 9, Page. 1-13
- Abstract
- 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 C-max and AUC(inf) 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 C-max 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 C-max and AUC(last) 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.
- URI
- https://www.mdpi.com/2075-4426/11/9/862https://repository.hanyang.ac.kr/handle/20.500.11754/168791
- ISSN
- 20754426
- DOI
- https://doi.org/10.3390/jpm11090862
- Appears in Collections:
- COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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