Abstract
Recent biochemical and pharmacological findings concerning tamoxifen (TMX) have proven that both the unchanged drug and the main metabolites, N-desmethyltamoxifen (NDT) and 4-hydroxytamoxifen (4OHT) are biologically active. An HPLC method based on on-line post-column UV irradiation with fluorescence detection is described. Optimized conditions allowed complete and rapid separation of TMX 4OHT, NDT and two other recently reported metabolites, Y and Z. This method was applied to plasma and cytosol drug and metabolite analyses. In plasma, from the moment of initial drug administration until the steady state (after 1 month or more of continuous oral TMX treatment), the values of NDT to TMX ratios were completely reversed: 22 to 215 in mean %, P less than 0.01. The presence of metabolites Y and Z is significant. 4OHT, hardly detectable at the first dose, was measured at the steady state with high interpatient variability. It is hypothesized that metabolite evolution with time may be due to auto-induction of drug metabolism. In cytosols, which were all obtained during continuous TMX treatment, the ratios between TMX and metabolites were comparable to those observed in plasma, but with greater interpatient variability. Metabolite Y was not detectable in cytosols. This variability was not linked to the levels of cytosolic oestradiol receptors before initiation of treatment.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Rights and permissions
About this article
Cite this article
Milano, G., Etienne, M., Frenay, M. et al. Optimised analysis of tamoxifen and its main metabolites in the plasma and cytosol of mammary tumours. Br J Cancer 55, 509–512 (1987). https://doi.org/10.1038/bjc.1987.103
Issue Date:
DOI: https://doi.org/10.1038/bjc.1987.103
This article is cited by
-
Activity Levels of Tamoxifen Metabolites at the Estrogen Receptor and the Impact of Genetic Polymorphisms of Phase I and II Enzymes on Their Concentration Levels in Plasma
Clinical Pharmacology & Therapeutics (2011)
-
TGFβ2 and TβRII are valid molecular biomarkers for the antiproliferative effects of tamoxifen and tamoxifen metabolites in breast cancer cells
Breast Cancer Research and Treatment (2007)
-
Tamoxifen activates CYP3A4 and MDR1 genes through steroid and xenobiotic receptor in breast cancer cells
Endocrine (2006)
-
The development of tamoxifen for breast cancer therapy: A tribute to the late Arthur L. Walpole
Breast Cancer Research and Treatment (1988)