CYP3A5*3 and SLCO1B1 c.521T>C Polymorphisms Influence the Pharmacokinetics of Atorvastatin and 2-Hydroxy Atorvastatinopen access
- Authors
- Park, Jin-Woo; Kim, Jong-Min; Lee, Hwa-Young; Noh, Jihyeon; Kim, Kyoung-Ah; Park, Ji-Young
- Issue Date
- Jul-2022
- Publisher
- Multidisciplinary Digital Publishing Institute (MDPI)
- Keywords
- atorvastatin; 2-hydroxy atorvastatin; SLCO1B1; CYP3A5; SNP
- Citation
- Pharmaceutics, v.14, no.7
- Indexed
- SCIE
SCOPUS
- Journal Title
- Pharmaceutics
- Volume
- 14
- Number
- 7
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/61311
- DOI
- 10.3390/pharmaceutics14071491
- ISSN
- 1999-4923
1999-4923
- Abstract
- There is a large variability in individual responses to atorvastatin administration. This study assessed the pharmacogenetic effects of solute carrier organic anion transporter family member 1B1 (SLCO1B1, c.388A>G and c.521T>C) and cytochrome P450 3A5 (CYP3A5, CYP3A5*3) genetic polymorphisms on the pharmacokinetics of atorvastatin and its active metabolite, 2-hydroxy (2-OH) atorvastatin, in 46 individuals who were administered a clinically used single oral dosage of 80 mg. The C-max and AUC of atorvastatin in CYP3A5*3/*3 carriers were 2.6- and 2.8-fold higher, respectively, than those in CYP3A5*1/*1 carriers, and similar results were observed for 2-OH atorvastatin pharmacokinetics. SLCO1B1 c.521T>C also increased the AUC of atorvastatin and 2-OH atorvastatin. The AUC ratio of atorvastatin and 2-OH atorvastatin were not affected by SLCO1B1 c.388A>G or c.521T>C, whereas CYP3A5*3 reduced the AUC ratio. In an analysis evaluating the simultaneous effect of the SLCO1B1 c.521T>C and CYP3A5*3 polymorphisms, SLCO1B1 c.521TT/CYP3A5*1/*1 carriers showed lower C-max and AUC values for atorvastatin and 2-OH atorvastatin than in individuals with the SLCO1B1 c.521T>C and/or CYP3A5*3 genotypes. Among the participants with the SLCO1B1 c.521TT genotype, the CYP3A5*3 carriers had a higher systemic exposure to atorvastatin and 2-OH atorvastatin than the CYP3A5*1/*1 carriers. Thus, SLCO1B1 c.521T>C and CYP3A5*3 polymorphisms affect the pharmacokinetics of atorvastatin and 2-OH atorvastatin.
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Collections - 2. Clinical Science > Department of Clinical Pharmacology and Toxicology > 1. Journal Articles
- 2. Clinical Science > Department of Neurology > 1. Journal Articles
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