RT Journal Article
SR Electronic
T1 Excretion of Hydroxylated Metabolites of Tamoxifen in Human Bile and Urine
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 4487
OP 4492
VO 25
IS 6C
A1 ELTON RICHARD KISANGA
A1 GUNNAR MELLGREN
A1 ERNST A. LIEN
YR 2005
UL http://ar.iiarjournals.org/content/25/6C/4487.abstract
AB 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. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved