Pharmacodynamics Antiandrogenic activity<unk>  acts as a selective competitive silent antagonist of the AR (IC50 = 412 nM), which prevents androgens like testosterone and DHT from activating the receptor. The affinity of<unk>  for the AR is about 1 to 4% of that of testosterone and is similar to that of bicalutamide and 2-hydroxyflutamide. Similarly to 2-hydroxyflutamide, but unlike bicalutamide,<unk>  is able to weakly activate the AR at high concentrations. It does not inhibit 5α-reductase. Like other NSAAs such as flutamide and bicalutamide,<unk> , without concomitant GnRH analogue therapy, increases serum androgen (by two-fold in the case of testosterone), estrogen, and prolactin levels due to inhibition of AR-mediated suppression of steroidogenesis via negative feedback on the hypothalamic–pituitary–gonadal axis. As such, though<unk>  is still effective as an antiandrogen as a monotherapy, it is given in combination with a GnRH analogue such as leuprorelin in prostate cancer to suppress androgen concentrations to castrate levels in order to attain maximal androgen blockade (MAB). Like flutamide and bicalutamide,<unk>  is able to cross the blood–brain barrier and has central antiandrogen actions. Cytochrome P450 inhibition<unk>  is known to inhibit several cytochrome P450 enzymes, including CYP1A2, CYP2C9, and CYP3A4, and can result in increased levels of medications that are metabolized by these enzymes. It has also been found to inhibit the enzyme CYP17A1 (17α-hydroxylase/17,20-lyase) in vitro and thus the biosynthesis of androgens. However,<unk>  monotherapy significantly increases testosterone levels in vivo, so the clinical significance of this finding is uncertain. Pharmacokinetics<unk>  has an elimination half-life of 23 to 87 hours, with a mean of 56 hours, or about two days; this allows for once-daily administration. Steady state (plateau) levels of the drug are attained after two weeks of administration with a dosage of 150 mg twice daily (300 mg/day total). It is metabolized by CYP2C19, with at least five metabolites. Virtually all of the antiandrogenic activity of<unk>  comes from the parent drug (as opposed to metabolites).
Nilutamide
Darolutamide
Acetothiolutamide
Apalutamide
Bicalutamide
Topilutamide
Flutamide
Enzalutamide