Excretion of hydroxylated metabolites of tamoxifen in human bile and urine.
The selective oestrogen-receptor modulator tamoxifen is the most commonly used drug against breast cancer. It has potent metabolites, such as 4-hydroxytamoxifen. Recently, the metabolite 4-hydroxy-N-desmethyltamoxifen has received increased attention as it may be a major contributor to the overall effects of tamoxifen. The excretion of tamoxifen and its metabolites was examined in a patient with biliary drainage after an oral dose of [14C]tamoxifen. During the first 10 days after oral dosing, 11.5, 26.7 and 24.7% of the radioactivity was excreted in the bile, urine and faeces, respectively. After deconjugation with beta-glucuronidase, the concentrations of tamoxifen and 4 of its metabolites were measured, and it was observed that the hydroxylated metabolites were excreted in the bile and urine. 4-Hydroxytamoxifen was the dominant compound, being detected during the first day of observation, whereas 4-hydroxy-N-desmethyltamoxifen was first observed in the urine and bile after 4 days. This is the first report on tamoxifen excretion in human bile and urine demonstrating that 4-hydroxytamoxifen may be a first-pass metabolite. In contrast, the potent metabolite 4-hydroxy-N-desmethyltamoxifen was first detected 4 days after administration of a single oral dose.
Kisanga
Elton Richard
ER
Section for Endocrinology, Institute of Medicine, University of Bergen, Bergen, Norway.
Mellgren
Gunnar
G
Lien
Ernst A
EA
D018931:Antineoplastic Agents, Hormonal / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000652:urine; D001646:Bile / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000652:urine; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000652:urine
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; C016601:afimoxifene