title: The influences of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin, in relation to CYP3A4 inhibition.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Research Division, National Institute of Food & Drug Safety Evaluation, Ministry of Food & Drug Safety, Cheongju, Republic of Korea.
authors.forename: Fen
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Clinical Research Division, National Institute of Food & Drug Safety Evaluation, Ministry of Food & Drug Safety, Cheongju, Republic of Korea.
authors.forename: Jong-Yeol
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Clinical Research Division, National Institute of Food & Drug Safety Evaluation, Ministry of Food & Drug Safety, Cheongju, Republic of Korea.
authors.forename: Ju-Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Clinical Research Division, National Institute of Food & Drug Safety Evaluation, Ministry of Food & Drug Safety, Cheongju, Republic of Korea.
authors.forename: Sunae
authors.initials: S
authors.lastname: Ryu
authors.affiliation: Clinical Research Division, National Institute of Food & Drug Safety Evaluation, Ministry of Food & Drug Safety, Cheongju, Republic of Korea.
authors.forename: Ze-Won
authors.initials: ZW
authors.lastname: Park
authors.affiliation: Clinical Research Division, National Institute of Food & Drug Safety Evaluation, Ministry of Food & Drug Safety, Cheongju, Republic of Korea.
authors.forename: Jong-Gu
authors.initials: JG
authors.lastname: Lee
authors.affiliation: Clinical Research Division, National Institute of Food & Drug Safety Evaluation, Ministry of Food & Drug Safety, Cheongju, Republic of Korea.
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Na
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Clinical Research Division, National Institute of Food & Drug Safety Evaluation, Ministry of Food & Drug Safety, Cheongju, Republic of Korea.
authors.forename: Woo-Yong
authors.initials: WY
authors.lastname: Oh
authors.affiliation: Clinical Research Division, National Institute of Food & Drug Safety Evaluation, Ministry of Food & Drug Safety, Cheongju, Republic of Korea.
authors.forename: Myeon-Woo
authors.initials: MW
authors.lastname: Chung
authors.affiliation: Clinical Research Division, National Institute of Food & Drug Safety Evaluation, Ministry of Food & Drug Safety, Cheongju, Republic of Korea.
authors.forename: Seung-Eun
authors.initials: SE
authors.lastname: Choi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000493:pharmacokinetics*; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics*; D019821:Simvastatin / Q000493:pharmacokinetics*; D016037:Single-Blind Method
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D065692:Cytochrome P-450 CYP3A Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; C503999:SLCO1B1 protein, human; D019821:Simvastatin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
keywords: ABCB1; SLCO1B1; amlodipine; pharmacogenomics; pharmacokinetics; simvastatin