Figure 5.

Pharmacokinetics and metabolism of SPRMs. Oral administration of SPRMs is frequently absorbed in the gastrointestinal tract and transported directly to the liver. All the SPRMs are primarily metabolized in the liver by cytochromes. Monodemethylated, didemethylated, and hydroxylated metabolites of mifepristone are produced by demethylation and hydroxylation metabolic pathway. The asoprisnil metabolites are produced by 17β-O-demethylation, which further conjugated with glutathione (SG). Like mifepristone, telapristone acetate and ulipristal acetate UPA produce mono and didemethylated metabolites, as well as hydroxylated metabolite. It has been proposed that vilaprisan undergoes reduction to produce hydroxyl derivatives, which further oxidate to produce various metabolites. All the SPRM metabolites are further catalyzed by CYP3A4 and aldoketoreductases. The unabsorbed parent compounds and metabolites are eliminated via urine and feces.