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Tamoxifen
- indication:For the treatment of breast cancer.
- pharmacologypharmacology:
- mechanism: Tamoxifen binds to estrogen receptors (ER), inducing a conformational change in the receptor. This results in a blockage or change in the expression of estrogen dependent genes. The prolonged binding of tamoxifen to the nuclear chromatin of these results in reduced DNA polymerase activity, impaired thymidine utilization, blockade of estradiol uptake, and decreased estrogen response. It is likely that tamoxifen interacts with other coactivators or corepressors in the tissue and binds with different estrogen receptors, ER-alpha or ER-beta, producing both estrogenic and antiestrogenic effects.
- toxicity: Signs observed at the highest doses following studies to determine LD<sub>50</sub> in animals were respiratory difficulties and convulsions.
- absorprion:
- halflife: Distribution t<sub>1/2</sub>=7 to 14 hours; Elimination t<sub>1/2</sub>=5 to 7 days; Elimination t<sub>1/2</sub> of N-desmethyl-tamoxifen=9-14 days.
- roouteelimination: The drug is excreted mainly as polar conjugates, with unchanged drug and unconjugated metabolites accounting for less than 30% of the total fecal radioactivity.
- volumedistribution:
- clearance: