title: A clinically significant interaction between warfarin and simvastatin is unique to carriers of the CYP2C9*3 allele.
abstract: BACKGROUND
  Simvastatin interacts with warfarin, but the strength of the interaction varies between individual patients, indicating a genetic predisposition.
  
  
  METHODS
  The influence of the CYP2C9*2 and CYP2C9*3 polymorphisms on the interaction between simvastatin and warfarin was analyzed in data from 1132 patients.
  
  
  RESULTS
  Simvastatin use reduced warfarin dose requirements by 29% in carriers of the CYP2C9*3 allele, compared with 5% in noncarriers. A regression model showed a significant influence of CYP2C9*3 on the drug-drug interaction, predicting a warfarin dose reduction of 25% in CYP2C9*3 heterozygotes and 43% in CYP2C9*3 homozygotes.
  
  
  CONCLUSIONS
  Our data indicate that the CYP2C9*3 polymorphism predisposes for a pharmacologic interaction between warfarin and simvastatin.
authors.affiliation: Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska University Hospital Huddinge, SE 141 86, Stockholm, Sweden. marine.andersson@karolinska.se
authors.forename: Marine L
authors.initials: ML
authors.lastname: Andersson
authors.forename: Erik
authors.initials: E
authors.lastname: Eliasson
authors.forename: Jonatan D
authors.initials: JD
authors.lastname: Lindh
mesh_terms: D000368:Aged; D000483:Alleles; D000925:Anticoagulants / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019821:Simvastatin / Q000627:therapeutic use*; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D000960:Hypolipidemic Agents; D014859:Warfarin; D019821:Simvastatin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases