Tamoxifen Inhibits Cytochrome P450 2C9 Activity in Breast Cancer Patients

• Published in: Journal of chemotherapy (Florence) 2006-08, Vol.18 (4), p.421-424
• Main Authors: Boruban, M.C., Yasar, U., Babaoglu, M.O., Sencan, O., Bozkurt, A.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiotensin II Type 1 Receptor Blockers - pharmacokinetics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antineoplastic Agents, Hormonal - pharmacology; Aryl Hydrocarbon Hydroxylases - antagonists & inhibitors; Aryl Hydrocarbon Hydroxylases - drug effects; Biological and medical sciences; Breast Neoplasms - drug therapy; Carboxylic Acids - metabolism; CYP2C9; Cytochrome P-450 CYP2C9; Drug Interactions; drug-drug interaction; Female; Gynecology. Andrology. Obstetrics; Humans; inhibition; Losartan - pharmacokinetics; Mammary gland diseases; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Tamoxifen; Tamoxifen - pharmacology; Tumors
• ISSN: 1120-009X; 1973-9478
• DOI: 10.1179/joc.2006.18.4.421

Tamoxifen has been reported to potentiate the anticoagulant effect of warfarin and also to increase the plasma level of phenytoin, which are mainly metabolized by CYP2C9. The aim of this study was to determine the influence of tamoxifen on CYP2C9 activity in vivo in humans. Thirteen breast cancer patients who would start tamoxifen following cytotoxic chemotherapy were enrolled in the study. A single oral dose of 25 mg losartan was given to the patients 2 days before and 2 weeks after starting tamoxifen therapy. Losartan and E3174 in 8-hour urine samples were measured by HPLC. Tamoxifen significantly increased the average urinary losartan/E3174 ratio from 0.73 (CI 95% =0.15-2.30) to 1.66 (CI 95% =0.68-5.20), after 2 weeks of treatment (p=0.002). Tamoxifen inhibited CYP2C9 activity in breast cancer patients within two weeks of its administration. The inhibition of CYP2C9 activity may be a possible explanation for the drug-drug interaction of tamoxifen with CYP2C9 substrates.