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Pharmacogenomics ; 18(5): 459-469, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28350522

ABSTRACT

AIM: To investigate the combined effects of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin and its active metabolite simvastatin acid, in relation to CYP3A4 inhibition. METHODS: We conducted a single-dose pharmacokinetic study of simvastatin in 26 healthy volunteers screened for their SLCO1B1 c.521T>C and ABCB1 c.1236C>T-2677G>T-3435C>T genotypes, with and without amlodipine pretreatment. The genetic effects and drug-interaction effect on simvastatin pharmacokinetic parameters were analyzed using a linear-mixed model. RESULTS: The SLCO1B1 c.521T>C variant significantly increased exposure to simvastatin acid by around 40% (p < 0.05), similar to that caused by the amlodipine pretreatment. The ABCB1 gene showed no influence on exposure to simvastatin or simvastatin acid. CONCLUSION: Only SLCO1B1, not ABCB1 genotype, is likely to be associated with simvastatin-induced myopathy. SLCO1B1 genotyping may be particularly beneficial in simvastatin users who are co-administered CYP3A4 inhibitors.


Subject(s)
Cytochrome P-450 CYP3A Inhibitors/pharmacokinetics , Cytochrome P-450 CYP3A/genetics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacokinetics , Liver-Specific Organic Anion Transporter 1/genetics , Simvastatin/pharmacokinetics , ATP Binding Cassette Transporter, Subfamily B/genetics , Genotype , Humans , Single-Blind Method
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