| Effects of the polymorphic MDR1 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects |
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Ji Hyun Sung, Seon-Sook Han, Mi-Eun Lee, Kwon-Soo Ha, Woo Jin Kim |
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| 건강성인에서 MDR1의 유전자 다형성에 따른 심바스타틴의 대사의 차이 |
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성지현, 한선숙, 이미은, 하권수, 김우진 |
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| Abstract |
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Background/Aims: Simvastatin has dramatically reduced cardiovascular disease due to elevated cholesterol. The human multidrug
resistance 1 gene (MDR1) encodes a 170-kDa transmembrane glycoprotein (P-glycoprotein), which plays an important role in
regulating the absorption, distribution, and excretion of simvastatin. To clarify the effects of the MDR1 gene polymorphism on simvastatin
pharmacokinetics, we investigated whether there is an association between genotype and the pharmacokinetic parameters
for simvastatin.
Methods: Thirty-one healthy unrelated Korean volunteers were genotyped for MDR1. Genomic DNA from blood was analyzed
using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Following an overnight fast, all
of the subjects took a single 60-mg oral dose of simvastatin. Venous blood samples were taken for 12 hours after the oral drug
intake. A statistical analysis of the MDR1 genotype and pharmacokinetic parameters of simvastatin was performed.
Results: The mean Tmax of the 1236TT genotype was significantly higher than that of CT and CC (p=0.02). The mean AUC0-12h of
3435TT was also significantly higher, compared with CT and CC (p=0.01). No significant difference was observed between the
MDR1 single nucleotide polymorphism (SNP) for G2677A/T and the pharmacokinetic parameters.
Conclusions: These findings suggest that polymorphic MDR1 genes are important in the inter-individual variation of the disposition
of simvastatin in humans. (Korean J Med 77:211-217, 2009) |
| Key Words:
Polymorphism, single nucleotide; P-glycoprotein; Pharmacokinetics; Simvastatin |
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