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

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 Univer...

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Autores principales:	Areepium N, Panomvana D, Rungwanonchai P, Sathaporn S, Voravud N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/35a04bea767f4e979462f164ba966c3e
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spelling	oai:doaj.org-article:35a04bea767f4e979462f164ba966c3e2021-12-02T01:19:08ZEffects of CYP2D6 and UGT2B7 polymorphisms on pharmacokinetics of tamoxifen in Thai breast cancer patients1179-1314https://doaj.org/article/35a04bea767f4e979462f164ba966c3e2013-08-01T00:00:00Zhttp://www.dovepress.com/effects-of-cyp2d6-and-ugt2b7-polymorphisms-on-pharmacokinetics-of-tamo-a14130https://doaj.org/toc/1179-1314N 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 CYP2D610 and UGT2B72 were 53% and 28%, respectively. Patients with CYP2D610/10 had lower END concentrations compared with CYP2D261/10 and CYP2D61/1 (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 CYP2D610/10, one with UGT2B72/2 had higher END concentrations compared against patients with UGT2B71/1 and UGT2B71/2 (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 cancerAreepium NPanomvana DRungwanonchai PSathaporn SVoravud NDove Medical PressarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol 2013, Iss default, Pp 73-78 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Areepium N Panomvana D Rungwanonchai P Sathaporn S Voravud N Effects of CYP2D6 and UGT2B7 polymorphisms on pharmacokinetics of tamoxifen in Thai breast cancer patients
description	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 CYP2D610 and UGT2B72 were 53% and 28%, respectively. Patients with CYP2D610/10 had lower END concentrations compared with CYP2D261/10 and CYP2D61/1 (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 CYP2D610/10, one with UGT2B72/2 had higher END concentrations compared against patients with UGT2B71/1 and UGT2B71/2 (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
format	article
author	Areepium N Panomvana D Rungwanonchai P Sathaporn S Voravud N
author_facet	Areepium N Panomvana D Rungwanonchai P Sathaporn S Voravud N
author_sort	Areepium N
title	Effects of CYP2D6 and UGT2B7 polymorphisms on pharmacokinetics of tamoxifen in Thai breast cancer patients
title_short	Effects of CYP2D6 and UGT2B7 polymorphisms on pharmacokinetics of tamoxifen in Thai breast cancer patients
title_full	Effects of CYP2D6 and UGT2B7 polymorphisms on pharmacokinetics of tamoxifen in Thai breast cancer patients
title_fullStr	Effects of CYP2D6 and UGT2B7 polymorphisms on pharmacokinetics of tamoxifen in Thai breast cancer patients
title_full_unstemmed	Effects of CYP2D6 and UGT2B7 polymorphisms on pharmacokinetics of tamoxifen in Thai breast cancer patients
title_sort	effects of cyp2d6 and ugt2b7 polymorphisms on pharmacokinetics of tamoxifen in thai breast cancer patients
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/35a04bea767f4e979462f164ba966c3e
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Effects of CYP2D6 and UGT2B7 polymorphisms on pharmacokinetics of tamoxifen in Thai breast cancer patients

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