AUTHOR=Kim Serim , Seo Jong Do , Yun Yeo-Min , Kim Hanah , Kim Tae-Eun , Lee Taeheon , Lee Tae-Rim , Lee Jun Hyung , Cho Eun-Hae , Ki Chang-Seok 

TITLE=Pharmacokinetics and Genetic Factors of Atorvastatin in Healthy Korean Subjects

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.836970

DOI=10.3389/fgene.2022.836970

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Statins are the most popular agents for the primary and secondary prevention of cardiovascular disease; however, the pharmacokinetic parameters and associated genetic factors in the Korean population have not been fully elucidated. This study explored the pharmacokinetic properties of atorvastatin and the association between genetic variations and atorvastatin pharmacokinetics in healthy Korean subjects.</p><p><bold>Methods:</bold> Atorvastatin (80 mg) was administered to 35 healthy Korean volunteers. Plasma levels of atorvastatin and its metabolites were measured sequentially using liquid chromatography-tandem mass spectrometry from 0 to 24 h after atorvastatin administration. Customized next-generation sequencing analysis was performed covering all coding exons of 15 genes, as well as 46 single-nucleotide variants in 29 genes related to statin pharmacokinetics.</p><p><bold>Results:</bold> The mean area under the concentration-time (AUC) and C<sub>max</sub> (maximum peak concentration) were 269.0 ng/ml∙h and 84.3 ng/ml, respectively, which were approximately two times higher than those reported in Caucasians. Genetic analysis revealed that eight genetic variants in <italic>ABCB1, ABCG2, APOA5, CETP</italic>, and <italic>CYP7A1</italic> contributed to the AUC of atorvastatin. The atorvastatin AUC<sub>0–24 h</sub> prediction model was developed based on age and eight genetic variants using multivariate linear regression (adjusted <italic>R</italic><sup>2</sup> = 0.878, <italic>p</italic> &lt; 0.0001).</p><p><bold>Conclusion:</bold> This study shows that the pharmacokinetic properties of atorvastatin in Koreans are different from those in Caucasians and that atorvastatin AUC<sub>0–24 h</sub> could be predicted based on age and eight genetic variants of <italic>ABCB1, ABCG2, APOA5, CETP,</italic> and <italic>CYP7A1</italic>.</p>