Screening study for genetic polymorphisms affecting pharmacokinetics of simvastatin
Translational and Clinical Pharmacology
;
: 43-54, 2016.
Article
in English
| WPRIM
| ID: wpr-158956
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Oxidoreductases
/
Pharmacogenetics
/
Plasma
/
Polymorphism, Genetic
/
Volunteers
/
DNA
/
Pharmacokinetics
/
Therapeutic Equivalency
/
Linear Models
/
Mass Screening
Type of study:
Diagnostic study
/
Prognostic study
/
Screening study
Limits:
Humans
/
Male
Language:
English
Journal:
Translational and Clinical Pharmacology
Year:
2016
Type:
Article
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