an increased anticoagulant effect, and for this reason, close monitoring of prothrombin time and dosage adjustment as necessary is recommended when bicalutamide is used in combination with these drugs. However, in spite of this, no conclusive evidence of an interaction between bicalutamide and other drugs was found in clinical trials of nearly 3,000 patients. Pharmacology Pharmacodynamics Antiandrogenic activity Bicalutamide acts as a highly selective competitive silent antagonist of the ( = 159–243 nM), the major biological target of the androgen sex hormones testosterone and , and hence is an antiandrogen. The activity of bicalutamide lies in the (R)-isomer. Due to its selectivity for the , bicalutamide does not interact importantly with other steroid hormone receptors and hence has no clinically relevant off-target hormonal activity (e.g., progestogenic, estrogenic, glucocorticoid, antimineralocorticoid). However, it has been reported that bicalutamide has weak affinity for the progesterone receptor (PR), where it is an antagonist, and hence it could have some antiprogestogenic activity. Bicalutamide does not inhibit 5α-reductase nor is known to inhibit other enzymes involved in androgen steroidogenesis (e.g., CYP17A1). Although it does not bind to the estrogen receptors (ERs), bicalutamide can increase estrogen levels secondarily to blockade when used as a monotherapy in males, and hence can have some indirect estrogenic effects in males. Bicalutamide neither suppresses nor inhibits androgen production in the body (i.e., it does not act as an antigonadotropin or androgen steroidogenesis inhibitor or lower androgen levels) and hence exclusively mediates its antiandrogenic effects by antagonizing the . In addition to the classical nuclear , bicalutamide has been assessed at the membrane androgen receptors (mARs) and found to act as a potent antagonist of ZIP9 ( = 66.3 nM), whereas it does not appear to interact with GPRC6A. The affinity of bicalutamide for the is relatively low as it is approximately 30 to 100 times lower than that of , which is 2.5- to 10-fold as potent as an agonist as testosterone in bioassays and is the main endogenous ligand of the receptor in the prostate gland. However, typical clinical dosages of bicalutamide result in circulating levels of the drug that are thousands of times higher than those of testosterone and , allowing it to powerfully prevent them from binding to and activating the receptor. This is especially true in the case of surgical or medical castration, in which testosterone levels in the circulation are approximately 95% reduced and levels in