Serum tamoxifen concentrations in the athymic nude mouse after three methods of administration

The athymic nude mouse has been used as an in vivo model for pharmacologic studies of the antiestrogen, tamoxifen. We have examined the steady-state serum tamoxifen concentrations achieved in mice with s.c. slow-release pellets, s.c. injections, and i.p. injections, in an attempt to identify a method that would yield serum levels similar to those observed in patients receiving tamoxifen therapy. Tamoxifen and tamoxifen metabolites were examined by a high-performance liquid chromatography assay which has a sensitivity of 8 ng/ml. Tamoxifen metabolites were not observed with any dose or schedule. After slow-release pellets containing 5 or 25 mg tamoxifen no tamoxifen was detectable, even after 2 weeks of treatment. Very low levels (0.07 microM) were found with 50-mg pellets. Tamoxifen was also not detected either with daily s.c. injections of 500 micrograms/mouse or with i.p. injections of 2.5 mg/kg. However, daily s.c. injections of 1000 micrograms or i.p. injections of 25, 50, or 100 mg/kg resulted in tamoxifen concentrations ranging from 0.21 to 0.51 microM which are similar to those observed in patients. Thus, clinically relevant tamoxifen concentrations can be achieved in the nude mouse with either of these methods of administration.