title: The UGT1A3*2 polymorphism affects atorvastatin lactonization and lipid-lowering effect in healthy volunteers.
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.
  
  
  CONCLUSIONS
  The UGT1A3*2 polymorphism is correlated with increased atorvastatin lactonization and may affect its lipid-lowering effect.
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: Sung Kweon
authors.initials: SK
authors.lastname: Cho
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Oh
authors.forename: Kyungsoo
authors.initials: K
authors.lastname: Park
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Park
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Chung
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D019540:Area Under Curve; D000069059:Atorvastatin; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D007783:Lactones / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D011758:Pyrroles / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D006538:Heptanoic Acids; D007783:Lactones; D008055:Lipids; D009363:Neoplasm Proteins; D011758:Pyrroles; D000069059:Atorvastatin; C122075:UDP-glucuronosyltransferase, UGT1A3; D014453:Glucuronosyltransferase