Tamoxifen metabolites in patients on long-term adjuvant therapy for breast cancer.
Serum concentrations of tamoxifen, 4-OH-tamoxifen, N-desmethyltamoxifen, and metabolites E and Y were assayed to assess the variation of tamoxifen-metabolism during short-term and long-term endocrine treatment for breast cancer. Once steady-state was achieved, serum levels of tamoxifen and its metabolites in individual patients were stable in the short (10 weeks) and long term (over 7 years) (coefficient of variation [CV], 10-15%), but the variation between individuals (CV 50-70%) was high. Serum tamoxifen and N-desmethyltamoxifen levels were not correlated with indices of obesity. Thus this does not explain the large variation between individuals. In addition to the metabolites that were measured, 4-hydroxy-N-desmethyltamoxifen was tentatively identified in patients' serum. Overall, this study demonstrated that the metabolites of tamoxifen are stable (i.e. no metabolic tolerance) for up to 10 years of drug administration.
Langan-Fahey
S M
SM
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
Tormey
D C
DC
Jordan
V C
VC
D001943:Breast Neoplasms / Q000188:drug therapy*; D004355:Drug Stability; D004965:Estrogen Antagonists / Q000097:blood; D006801:Humans; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D013997:Time Factors
D004965:Estrogen Antagonists; D013629:Tamoxifen; C016601:afimoxifene; C052626:ICI 142269; C028787:N-desmethyltamoxifen