Sex-related pharmacokinetic differences and mechanisms of metapristone (RU486 metabolite).

ABSTRACT: Metapristone is the primary metabolite of the abortifacient mifepristone (RU486), and is being developed as a safe and effective cancer metastatic chemopreventive agent for both sexes. Here, we systematically investigated the sex-related pharmacokinetics of metapristone in both rats and dogs, and explored the related mechanisms of actions. Administration of metapristone to rats and dogs showed that plasma concentrations of metapristone (AUC, C max ) were significantly higher in female dogs and rats than in males. The sex-related differences in pharmacokinetics become more significant after ten consecutive days of oral administration. Female liver microsomes metabolized metapristone significantly slower than the male ones. The results from P450 reaction phenotyping using recombinant cDNA-ex

SUBMITTER: Chen W 

PROVIDER: S-EPMC5719405 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature