PF-02413873 is a selective nonsteroidal progesterone receptor (PR) antagonist. PF-02413873 is turned over by recombinant human P450s, with CYP3A4 displaying the highest turnover of those enzymes tested. PF-02413873 possessed low oral clearance in hum...
an with a pharmacokinetic profile consistent with a once-daily dosing schedule. The pharmacological mode of action of PF-02413873 seems to differ from the founding member of the class of steroidal PR antagonists RU-486. Exposure-effect data from studies in the cynomolgus macaque, however, demonstrated that PF-02413873 reduced endometrial functionalis thickness to a comparable degree to RU-486 and this effect was accompanied by a decrease in proliferation rate for both RU-486 and high-dose PF-02413873. PF-02413873blocked the follicular phase increase in endometrial thickness, the midcycle luteinizing hormone surge, and elevation in estradiol in a dose-dependent fashion compared with placebo. PF-02413873 had been in phase I clinical trial for the treatment of endometriosis. However, this development was discontinued.
