Decreased warfarin clearance associated with the CYP2C9 R150H (*8) polymorphism

Clin Pharmacol Ther. 2012 Apr;91(4):660-5. doi: 10.1038/clpt.2011.269. Epub 2012 Feb 29.


The cytochrome P450 (CYP) 2C9 R150H (*8) allele occurs commonly in African Americans and is associated with lower warfarin dose requirements. We conducted a pharmacokinetic study to examine whether the CYP2C9*8 allele impacts warfarin clearance in African-American patients. We also conducted an in vitro kinetic study of S-warfarin 7-hydroxylation using complementary DNA (cDNA)-expressed CYP2C9 enzymes. We observed a 30% reduction in the unbound oral clearance of S-warfarin and a 25% lower R- to S-warfarin plasma concentration ratio in patients with the CYP2C9*8 allele (n = 12) as compared to CYP2C9*1 homozygotes (n = 26). Consistent with these findings, the in vitro intrinsic clearance of S-warfarin was 30% lower with the cDNA-expressed R150H protein as compared to the wild-type protein. These data show that the R150H variant protein expressed by the CYP2C9*8 allele is associated with lower S-warfarin clearance. This finding provides clinical and experimental evidence to explain the lower warfarin dose requirements in patients with the CYP2C9*8 allele.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Black or African American / genetics
  • Cytochrome P-450 CYP2C9
  • Female
  • Genetic Variation / genetics
  • Hep G2 Cells
  • Humans
  • Male
  • Metabolic Clearance Rate / genetics
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Warfarin / pharmacokinetics*


  • Warfarin
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases