Screening study for genetic polymorphisms affecting pharmacokinetics of simvastatin

Sohee Im; Bo Hyung Kim; Kidong Lee; Kyu Bum Kwack; Sung Vin Yim

doi:10.12793/tcp.2016.24.1.43

Screening study for genetic polymorphisms affecting pharmacokinetics of simvastatin

Sohee Im, Bo Hyung Kim, Kidong Lee, Kyu Bum Kwack, Sung Vin Yim

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

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.

Original language	English
Pages (from-to)	43-54
Number of pages	12
Journal	Translational and Clinical Pharmacology
Volume	24
Issue number	1
DOIs	https://doi.org/10.12793/tcp.2016.24.1.43
Publication status	Published - 2016

Bibliographical note

Publisher Copyright:
© 2016 Translational and Clinical Pharmacology.

Keywords

Pharmacogenomics
Pharmacokinetics
Simvastatin
Single nucleotide polymorphism

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10.12793/tcp.2016.24.1.43

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title = "Screening study for genetic polymorphisms affecting pharmacokinetics of simvastatin",

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 Cmax, 135 significant SNPs (P < 0.01) in Tmax and 85 significant SNPs (P < 0.01) in AUCinf from whole genome analysis. In particular, we found that the ABCC2 gene had a significant effect on Cmax and AUCinf. These results could provide information of possible candidate genes for personalized simvastatin therapy.",

keywords = "Pharmacogenomics, Pharmacokinetics, Simvastatin, Single nucleotide polymorphism",

author = "Sohee Im and Kim, {Bo Hyung} and Kidong Lee and Kwack, {Kyu Bum} and Yim, {Sung Vin}",

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year = "2016",

doi = "10.12793/tcp.2016.24.1.43",

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AU - Im, Sohee

AU - Kim, Bo Hyung

AU - Lee, Kidong

AU - Kwack, Kyu Bum

AU - Yim, Sung Vin

PY - 2016

Y1 - 2016

N2 - 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 Cmax, 135 significant SNPs (P < 0.01) in Tmax and 85 significant SNPs (P < 0.01) in AUCinf from whole genome analysis. In particular, we found that the ABCC2 gene had a significant effect on Cmax and AUCinf. These results could provide information of possible candidate genes for personalized simvastatin therapy.

AB - 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 Cmax, 135 significant SNPs (P < 0.01) in Tmax and 85 significant SNPs (P < 0.01) in AUCinf from whole genome analysis. In particular, we found that the ABCC2 gene had a significant effect on Cmax and AUCinf. These results could provide information of possible candidate genes for personalized simvastatin therapy.

KW - Pharmacogenomics

KW - Pharmacokinetics

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KW - Single nucleotide polymorphism

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EP - 54

JO - Translational and Clinical Pharmacology

JF - Translational and Clinical Pharmacology

IS - 1

ER -

Screening study for genetic polymorphisms affecting pharmacokinetics of simvastatin

Abstract

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Keywords

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