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The UGT1A3*2 polymorphism affects atorvastatin lactonization and lipid-lowering effect in healthy volunteers

Authors
 Cho, Sung Kweon  ;  Oh, Eun Sil  ;  Park, Kyungsoo  ;  Park, Min Soo  ;  Chung, Jae Yong 
Citation
 Pharmacogenetics and Genomics, Vol.22(8) : 598-605, 2012 
Journal Title
 Pharmacogenetics and Genomics 
ISSN
 1744-6872 
Issue Date
2012
Abstract
OBJECTIVE: We investigated whether the UGT1A3 polymorphisms play an important role in interindividual variations in atorvastatin lactonization and lipid-lowering effect. METHODS: Twenty-three healthy volunteers were administered atorvastatin 20 mg once daily for 14 days. Serum levels of lipids were measured before and 7, 13, 14, 15, 21, and 28 days after the initial dosing. Blood samples for pharmacokinetic analysis were collected up to 48 h after the last dose. RESULTS: The UGT1A3*2 and UGT1A1*28 polymorphism had a perfect linkage in the participants. Lactone formation was significantly higher in the UGT1A3*2 carriers. The areas under the curve of atorvastatin lactone and 2-hydroxyatorvastatin lactone were 72 and 160% higher in individuals with UGT1A3*2/*2 than UGT1A3*1/*1, respectively. The maximum percent decreases in the total and the low-density lipoprotein cholesterol from baseline in UGT1A3*2 carriers were 29 and 18% less than the UGT1A3*2 noncarriers, respectively. CONCLUSION: The UGT1A3*2 polymorphism is correlated with increased atorvastatin lactonization and may affect its lipid-lowering effect.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91662
DOI
10.1097/FPC.0b013e3283544085
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실)
Yonsei Authors
박경수(Park, Kyung Soo) ; 박민수(Park, Min Soo) ; 정재용(Chung, Jae Yong) ; 조성권(Cho, Sung Kweon)
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