However, unlike enzalutamide, bicalutamide has not been found to be associated with seizures or other related adverse central effects, so the clinical relevance of this finding is uncertain. Pharmacokinetics
Though its absolute bioavailability in humans is unknown, bicalutamide is known to be extensively and well-absorbed. Its absorption is not affected by food. The absorption of bicalutamide is linear at doses up to 150 mg/day and is saturable at doses above this, with no further increases in steady-state levels of bicalutamide occurring at doses above 300 mg/day. Whereas absorption of (R)-bicalutamide is slow, with levels peaking at 31 to 39 hours after a dose, (S)-bicalutamide is much more rapidly absorbed. Steady-state concentrations of the drug are reached after 4 to 12 weeks of treatment independently of dosage, with a 10- to 20-fold progressive accumulation in levels of (R)-bicalutamide. The long time to steady-state levels is the result of bicalutamides very long elimination half-life.The tissue distribution of bicalutamide is not well-characterized. The amount of bicalutamide in semen that could potentially be transferred to a female partner during sexual intercourse is low and is not thought to be important. Based on animal studies with rats and dogs it was thought that bicalutamide could not cross the blood–brain barrier and hence could not enter the brain. As such, it was initially thought to be a peripherally selective antiandrogen.
However, in spite of the fact bicalutamide is metabolized by CYP3A4, there is no evidence of clinically significant drug interactions when bicalutamide at a dosage of 150 mg/day or less is co-administered with drugs that inhibit or induce cytochrome P450 enzyme activity.In-vitro studies suggest that bicalutamide may be able to inhibit CYP3A4 and, to a lesser extent, CYP2C9, CYP2C19, and CYP2D6. Conversely, animal studies suggest that bicalutamide may induce cytochrome P450 enzymes. In a clinical study, bicalutamide co-administered with the CYP3A4 substrate midazolam caused only a small and statistically non-significant increase in midazolam levels (+27%) presumably due to CYP3A4 inhibition. However, this was well below the increases with potent CYP3A4 inhibitors like ketoconazole (+1500%), itraconazole (+1000%), and erythromycin (+350%), and is considered to not be clinically important. There is no indication of clinically significant enzyme inhibition or induction with bicalutamide at doses of 150 mg/day or below.Because bicalutamide circulates at relatively high concentrations and is highly protein-bound, it has the potential to displace other highly protein-bound drugs like warfarin, phenytoin, theophylline, and aspirin from plasma binding proteins. This could, in turn, result in increased free concentrations of such drugs and increased effects and/or side effects, potentially necessitating dosage adjustments. Bicalutamide has specifically been found to displace coumarin anticoagulants like warfarin from their plasma binding proteins (namely albumin) in vitro, potentially resulting in 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.