Identification of tamoxifen metabolites in human Hep G2 cell line, human liver homogenate, and patients on long-term therapy for breast cancer.
The metabolism of tamoxifen was examined in human liver homogenate and human Hep G2 cell line preparations by LC/electro spray ionization/MS. Several metabolites were detected in the human liver homogenate extracts, namely N-didesmethyltamoxifen (metabolite I), alpha-hydroxytamoxifen (metabolite II), 4-hydroxytamoxifen (metabolite III), N-desmethyltamoxifen (metabolite IV), and tamoxifen N-oxide (metabolite V). Metabolites II, III, IV, and V were observed in the samples after incubating tamoxifen with the human Hep G2 cell line. When these results were compared with the metabolic profiles in patients, apart from metabolites I-V, alpha-hydroxy-N-desmethyltamoxifen (VI) and 4-hydroxy N-desmethyltamoxifen (VII) were present in all the plasma samples. In addition, in patients who had received tamoxifen treatment daily for > 6 months, several minor metabolites were detected, namely 4-hydroxytamoxifen N-oxide (metabolite VIII) and two dihydroxylated analogs (metabolites IX and X). The precise positions of the hydroxylation have yet to be determined.
Poon
G K
GK
CRC Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, UK.
Walter
B
B
Lønning
P E
PE
Horton
M N
MN
McCague
R
R
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D013629:Tamoxifen / Q000378:metabolism* / Q000627:therapeutic use; D013997:Time Factors; D014407:Tumor Cells, Cultured
D013629:Tamoxifen