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Effects of CYP2D6 and UGT2B7 polymorphisms on pharmacokinetics of tamoxifen in Thai breast cancer patients

Authors Areepium, Panomvana D, Rungwanonchai, Satthaporn S, Voravud

Received 24 April 2013

Accepted for publication 9 July 2013

Published 22 August 2013 Volume 2013:5 Pages 73—78


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

N Areepium,1 D Panomvana,1 P Rungwanonchai,1 S Sathaporn,2 N Voravud3

1Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 2Department of Surgery, Phramongkutklao Hospital, Bangkok, 3Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

Purpose: 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).
Conclusion: 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.

Keywords: tamoxifen, pharmacogenomics, CYP2D6, UGT2B7, breast cancer

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