Pharmacokinetics of endoxifen and tamoxifen in female mice: implications for comparative in vivo activity studies.

ABSTRACT:

Background

Reduced CYP2D6 metabolism and low Z-endoxifen (ENDX) concentrations may increase the risk of breast cancer recurrence in tamoxifen (TAM)-treated women. Little is known regarding the differences between TAM and ENDX murine pharmacokinetics or the effect of administration route on plasma concentrations of each drug.

Methods

The pharmacokinetics of TAM and ENDX were characterized in female mice.

Results

For subcutaneous [s.c.] and oral TAM (4, 10 and 20 mg/kg), TAM AUC increased in a linear manner, but concentrations of the active metabolites [ENDX and 4-hydroxytamoxifen (4HT)] remained low. For oral TAM (20 mg), 4HT concentrations were tenfold greater (>25 ng/ml) than achievable in TAM-treated humans. Both oral (10-200 mg/kg) and s.c. (2.5-25 mg/kg) ENDX·HCl

SUBMITTER: Reid JM 

PROVIDER: S-EPMC4343319 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature