Abstract
The athymic nude mouse has been used as an in vivo model for pharmacologic studies of the antiestrogen, tamoxifen. We hav 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 μM) were found with 50-mg pellets. Tamoxifen was also not detected either with daily s. c. injections of 500 μg/mouse or with i. p. injections of 2.5 mg/kg. However, daily s. c. injections of 1000 μg or i. p. injections of 25, 50, o4 100 mg/kg resulted in tamoxifen concentrations ranging from 0.21 to 0.51 μM 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 316-318 |
| Number of pages | 3 |
| Journal | Cancer Chemotherapy and Pharmacology |
| Volume | 20 |
| Issue number | 4 |
| DOIs | |
| State | Published - Dec 1987 |
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ASJC Scopus subject areas
- Pharmacology
- Oncology
- Cancer Research
Cite this
Serum tamoxifen concentrations in the athymic nude mouse after three methods of administration. / DeGregorio, Michael W.; Wilbur, Bruce J.; Coronado, Ester; Osborne, C. Kent.
In: Cancer Chemotherapy and Pharmacology, Vol. 20, No. 4, 12.1987, p. 316-318.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Serum tamoxifen concentrations in the athymic nude mouse after three methods of administration
AU - DeGregorio, Michael W.
AU - Wilbur, Bruce J.
AU - Coronado, Ester
AU - Osborne, C. Kent
PY - 1987/12
Y1 - 1987/12
N2 - The athymic nude mouse has been used as an in vivo model for pharmacologic studies of the antiestrogen, tamoxifen. We hav 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 μM) were found with 50-mg pellets. Tamoxifen was also not detected either with daily s. c. injections of 500 μg/mouse or with i. p. injections of 2.5 mg/kg. However, daily s. c. injections of 1000 μg or i. p. injections of 25, 50, o4 100 mg/kg resulted in tamoxifen concentrations ranging from 0.21 to 0.51 μM 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.
AB - The athymic nude mouse has been used as an in vivo model for pharmacologic studies of the antiestrogen, tamoxifen. We hav 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 μM) were found with 50-mg pellets. Tamoxifen was also not detected either with daily s. c. injections of 500 μg/mouse or with i. p. injections of 2.5 mg/kg. However, daily s. c. injections of 1000 μg or i. p. injections of 25, 50, o4 100 mg/kg resulted in tamoxifen concentrations ranging from 0.21 to 0.51 μM 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.
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U2 - 10.1007/BF00262583
DO - 10.1007/BF00262583
M3 - Article
C2 - 3690805
AN - SCOPUS:0023501880
VL - 20
SP - 316
EP - 318
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
SN - 0344-5704
IS - 4
ER -