Transl Clin Pharmacol.  2016 Mar;24(1):43-54. 10.12793/tcp.2016.24.1.43.

Screening study for genetic polymorphisms affecting pharmacokinetics of simvastatin

• Im S
• Kim BH
• Lee K
• Kwack K
• Yim SV

• KMID: 2383599
• DOI: http://doi.org/10.12793/tcp.2016.24.1.43

Abstract

Simvastatin reduces plasma cholesterol by inhibiting HMG-CoA reductase (HMGR) and is widely used in the treatment of hypercholesterolemia. To screening the possible genetic factors affecting the pharmacokinetics (PK) of simvastatin, 35 male Korean volunteers were enrolled from two separate bioequivalence studies. Each subject was administered 20 mg simvastatin and reference drug PK parameters were used. We used Illumina Human610Quad v1.0 DNA Analysis BeadChip for whole genome SNPs analysis and whole genome genotyping data was processed by linear regression analysis for PK parameters of drug metabolizing enzymes and transporters. We found 145 significant SNPs (P < 0.01) in C(max), 135 significant SNPs (P < 0.01) in T(max) and 85 significant SNPs (P < 0.01) in AUC(inf) from whole genome analysis. In particular, we found that the ABCC2 gene had a significant effect on C(max) and AUC(inf). These results could provide information of possible candidate genes for personalized simvastatin therapy.

Keyword

Pharmacogenomics; Simvastatin; Pharmacokinetics; Single nucleotide polymorphism

MeSH Terms

Cholesterol
DNA
Genome
Humans
Hypercholesterolemia
Linear Models
Male
Mass Screening*
Oxidoreductases
Pharmacogenetics
Pharmacokinetics*
Plasma
Polymorphism, Genetic*
Polymorphism, Single Nucleotide
Simvastatin*
Therapeutic Equivalency
Volunteers
Cholesterol
DNA
Oxidoreductases
Simvastatin

Reference

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