In contrast to the SAA spironolactone, bicalutamide does not have antimineralocorticoid effects, and hence is not associated with hyperkalemia, urinary frequency, dehydration, hypotension, or other related side effects. In women, unlike CPA and spironolactone, bicalutamide does not produce menstrual irregularity or amenorrhea and does not interfere with ovulation or fertility. Overdose
A single oral dose of bicalutamide in humans that results in symptoms of overdose or that is considered to be life-threatening has not been established. Dosages of up to 600 mg/day have been well tolerated in clinical trials, and it is notable that there is a saturation of absorption with bicalutamide such that circulating levels of its active (R)-enantiomer do not further increase above a dosage of 300 mg/day. Overdose is considered unlikely to be life-threatening with bicalutamide or other first-generation NSAAs (i.e., flutamide and nilutamide). A massive overdose of nilutamide (13 grams, or 43 times the normal maximum 300 mg/day clinical dosage) in a 79-year-old man was uneventful, producing no clinical signs, symptoms, or toxicity. There is no specific antidote for bicalutamide or NSAA overdose, and treatment should be based on symptoms, if any are present. Interactions
Bicalutamide is almost exclusively metabolized by CYP3A4. As such, its levels in the body may be altered by inhibitors and inducers of CYP3A4. (For a list of CYP3A4 inhibitors and inducers, see here.)
The glucuronide conjugates of bicalutamide and its metabolites are eliminated from the circulation rapidly, unlike unconjugated bicalutamide.The pharmacokinetics of bicalutamide are not affected by consumption of food, a persons age or body weight, renal impairment, or mild-to-moderate hepatic impairment. However, steady-state levels of bicalutamide are higher in Japanese individuals than in white people. Chemistry
Bicalutamide is a racemic mixture consisting of equal proportions of enantiomers (R)-bicalutamide (dextrorotatory) and (S)-bicalutamide (levorotatory). Its systematic name (IUPAC) is (RS)-N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide. The compound has a chemical formula of C18H14F4N2O4S, a molecular weight of 430.373 g/mol, and is a fine white to off-white powder.The acid dissociation constant (pKa) of bicalutamide is approximately 12. It is a highly lipophilic compound (log P = 2.92). At 37 °C (98.6 °F), or normal human body temperature, bicalutamide is practically insoluble in water (4.6 mg/L), acid (4.6 mg/L at pH 1), and alkali (3.7 mg/L at pH 8). In organic solvents, it is slightly soluble in chloroform and absolute ethanol, sparingly soluble in methanol, and freely soluble in acetone and tetrahydrofuran.Bicalutamide is a synthetic and nonsteroidal compound which was derived from flutamide. It is a bicyclic compound (has two rings) and can be classified as and has variously been referred to as an anilide (N-phenylamide) or aniline, a diarylpropionamide, and a toluidide. Analogues
First-generation NSAAs including bicalutamide, flutamide, and nilutamide are all synthetic, nonsteroidal anilide derivatives and structural analogues of each other. Bicalutamide is a diarylpropionamide while flutamide is a monoarylpropionamide and nilutamide is a hydantoin. Bicalutamide and flutamide, though not nilutamide, can also be classified as toluidides.