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Effects of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of atorvastatin and 2-hydroxyatorvastatin in healthy Korean subjects

 박영아  ;  김정은  ;  남궁란  ;  박민수  ;  박국인  ;  이철 
 International Journal of Clinical Pharmacology and Therapeutics, Vol.48(1) : 36-45, 2010 
Journal Title
 International Journal of Clinical Pharmacology and Therapeutics 
Issue Date
OBJECTIVE: This study aimed to evaluate the effect of genetic polymorphisms of SLCO1B1 and ABCB1 on the pharmacokinetics of atorvastatin and its metabolites. METHODS: 290 Koreans were genotyped for SLCO1B1, ABCB1 and CYP3A5, and 28 subjects were selected for the pharmacokinetic study. Each subject received a single oral dose of 20 mg atorvastatin and blood samples were collected up to 48 hr after dosing. The relationship between the genotypes and atorvastatin pharmacokinetics was examined. RESULTS: For SLCO1B1 genotypes, the mean area under the concentration-time curve from time 0 to infinity (AUC0-infinity) of atorvastatin was 148.2 ng x hr/ml for *15/*15 subjects (n = 3), which was significantly larger than for 1a/*15 and *1b/*15 (n = 8) (80.7 ng x hr/ml, p = 0.0121) and also larger than for *1a/*1a, *1a/*1b and *1b/*1b (n = 17) (66.3 ng x hr/ml, p = 0.0018). The mean AUC0-infinity of 2-hydroxyatorvastatin for *15/*15 was also larger than in *1a/*1a, *1a/*1b and *1b/*1b (p = 0.012). In lactone forms, no significant pharmacokinetic difference was found among the genotypes. For ABCB1 genotypes, the half-lives of atorvastatin, atorvastatin lactone, 2-hydroxyatorvastatin and 2-hydroxyatorvastatin lactone were significantly longer in c.2677TT-c.3435TT (n = 3) vs. c.2677GG-c.3435CC and c.2677GT-c.3435CT (n = 10), yielding p = 0.049, 0.007, 0.007 and 0.007, respectively. CONCLUSION: This study shows that the SLCO1B1*15 allele may be associated with the individual difference in the AUC0-infinity of atorvastatin whereas the ABCB1 TT-TT diplotype may affect the elimination half-life of the drug in the Korean population.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
이민구(Lee, Min Goo) ORCID logo https://orcid.org/0000-0001-7436-012X
이윤정(Lee, Yoon Jung)
임아영(Lim, Lay Ahyoung)
장성복(Jang, Seong Bok)
정재용(Chung, Jae Yong)
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