Tumor and serum tamoxifen concentrations in the athymic nude mouse

The athymic nude mouse has been used as an in vivo model for pharmacologic studies of the antiestrogen, tamoxifen. Serum and tumor tamoxifen and metabolite concentrations were examined during and after 100 and 1000 micrograms/day doses injected s.c. Tamoxifen and tamoxifen metabolites were quantitated by high-performance liquid chromatography. Tamoxifen was detected in tumors after a dose of 100 micrograms/day, although serum concentrations were not detected. At a dose of 1000 micrograms/day, tumor tamoxifen and its active metabolites were detected in high concentrations ranging up to greater than 6 mmol/g tissue. Serum tamoxifen metabolites were not detected at either dose. In summary, high doses of tamoxifen were required in the nude mouse to obtain clinically relevant serum concentrations, and significant tumor levels were achieved at doses that resulted in undetectable serum levels. The relationship between serum tamoxifen concentrations, tumor tamoxifen levels, and the biologic activity of the drug requires further study.