Genetics
Atorvastatin exposure is about twice as high in healthy Korean volunteers as in Caucasians, partly explained by eight variants including one in CETP (Front Genet 2022)
Original title: Pharmacokinetics and Genetic Factors of Atorvastatin in Healthy Korean Subjects
Thirty-five healthy Korean volunteers received a single 80 mg dose of atorvastatin, with plasma drug and metabolite levels measured over 24 hours and sequencing covering statin-pharmacokinetics-related genes. Mean atorvastatin exposure (AUC 269.0 ng/mL times h, Cmax 84.3 ng/mL) was roughly twice that previously reported in Caucasians. Eight genetic variants across ABCB1, ABCG2, APOA5, CETP and CYP7A1 contributed to atorvastatin AUC, and a prediction model combining age with these eight variants explained the AUC with an adjusted R-squared of 0.878. The authors conclude atorvastatin pharmacokinetics differ meaningfully in Koreans compared with Caucasians and can be partly predicted from age and this small panel of genetic variants, of which CETP is one contributor without an individually reported effect size.
Original abstract
Background: 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. Methods: 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. Results: The mean area under the concentration-time (AUC) and Cmax (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 ABCB1, ABCG2, APOA5, CETP, and CYP7A1 contributed to the AUC of atorvastatin. The atorvastatin AUC0-24 h prediction model was developed based on age and eight genetic variants using multivariate linear regression (adjusted R 2 = 0.878, p < 0.0001). Conclusion: This study shows that the pharmacokinetic properties of atorvastatin in Koreans are different from those in Caucasians and that atorvastatin AUC0-24 h could be predicted based on age and eight genetic variants of ABCB1, ABCG2, APOA5, CETP, and CYP7A1.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.