The influences of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin, in relation to CYP3A4 inhibition
| Autor: | Seung-Eun Choi, Myeon-Woo Chung, Zewon Park, Jong-Yeol Choi, Jong-Gu Lee, Seok-Yong Lee, Woo-Yong Oh, Fen Jiang, Ju Hyun Lee, Sunae Ryu, Han-Sung Na |
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| Rok vydání: | 2017 |
| Předmět: |
Simvastatin
ATP Binding Cassette Transporter Subfamily B Genotype Pharmacology 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Pharmacokinetics polycyclic compounds Genetics medicine Cytochrome P-450 CYP3A Humans Single-Blind Method cardiovascular diseases Amlodipine Myopathy Active metabolite biology CYP3A4 business.industry Liver-Specific Organic Anion Transporter 1 organic chemicals nutritional and metabolic diseases 030220 oncology & carcinogenesis biology.protein Molecular Medicine Cytochrome P-450 CYP3A Inhibitors lipids (amino acids peptides and proteins) medicine.symptom Hydroxymethylglutaryl-CoA Reductase Inhibitors SLCO1B1 business medicine.drug |
| Zdroj: | Pharmacogenomics. 18(5) |
| ISSN: | 1744-8042 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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