In:
Pharmacogenomics, Future Medicine Ltd, Vol. 18, No. 5 ( 2017-04), p. 459-469
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.
Type of Medium:
Online Resource
ISSN:
1462-2416
,
1744-8042
DOI:
10.2217/pgs-2016-0199
Language:
English
Publisher:
Future Medicine Ltd
Publication Date:
2017
SSG:
15,3
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