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The relative binding affinities (relative to progesterone) of mifepristone and it's a 3 main metabolites to the human uterine progesterone receptor have been determined by Lahteenmaki et al. These are tabulated below:-
Compound |
Relative Affinity %* |
| Mifepristone Progesterone RU42633 RU42698 RU42848 |
323 100 50 36 21 |
| * Relative to progesterone (=100%) | |
The binding affinities of the metabolites of the uterine progesterone receptor are about 10 to 20% that of mifepristone. A study by Deraedt et al calculated the abortive effect of the 3 main metabolites in the rat and showed that ED100 (effective dose) was 3x greater for the monodemethylated and hydroxylated compounds than for mifepristone itself. The didemethylated compound on the other hand, was ineffective. When a single, high dose of mifepristone was administered cumulative total plasma concentration of the 3 metabolites added together greatly exceeds that of mifepristone alone. This suggest that the metabolites may have a significant role in the overall antiprogesterone action of the drug.