title: Effects of CYP2D6 and UGT2B7 polymorphisms on pharmacokinetics of tamoxifen in Thai breast cancer patients.
abstract: OBJECTIVE
  The objective of this study was to evaluate the impact of CYP2D6 and UGT2B7 polymorphisms on tamoxifen (TAM) pharmacokinetics in Thai breast cancer patients.
  
  
  METHODS
  Thai female breast cancer patients treated with TAM were included in the study. Patients were genotyped for CYP2D6 and UGT2B7 polymorphism, and plasma levels of TAM and its potent active metabolite endoxifen (END), at steady state, were identified.
  
  
  RESULTS
  Fifty-nine female breast cancer patients were included in the study. The average age was 50 ± 9.3 years old; 76% were premenopausal and 85% had estrogen receptor-positive breast cancer. The allele frequencies of CYP2D6*10 and UGT2B7*2 were 53% and 28%, respectively. Patients with CYP2D6*10/*10 had lower END concentrations compared with CYP2D26*1/*10 and CYP2D6*1/*1 (9.62 ng/mL versus 15.67 ng/mL and 21.55 ng/mL, respectively, P = 0.045). Polymorphisms of UGT2B7 alone did not have any impact on TAM metabolism. However, among 20 patients with CYP2D6*10/*10, one with UGT2B7*2/*2 had higher END concentrations compared against patients with UGT2B7*1/*1 and UGT2B7*1/*2 (31.36 ng/mL versus 7.86 ng/mL, respectively, P = 0.023).
  
  
  CONCLUSIONS
  Results from this study confirmed the impacts of CYP2D6 polymorphisms on the pharmacokinetics of TAM, while UGT2B7 polymorphisms tended to have impact on TAM metabolism in patients with homozygous CYP2D6*10.
authors.affiliation: Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: N
authors.initials: N
authors.lastname: Areepium
authors.affiliation: Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: D
authors.initials: D
authors.lastname: Panomvana
authors.affiliation: Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Rungwanonchai
authors.affiliation: Department of Surgery, Phramongkutklao Hospital, Bangkok, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Sathaporn
authors.affiliation: Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: N
authors.initials: N
authors.lastname: Voravud
keywords: CYP2D6; UGT2B7; breast cancer; pharmacogenomics; tamoxifen