Bicalutamide dosing

Flutamide is an androgen receptor antagonist that achieves peak concentrations approximately 2 to 4 hours after an oral dose. Flutamide is metabolized extensively, with a terminal half-life of about 8 hours. Bicalutamide achieves peak concentrations approximately 6 hours after the dose, with a terminal half-life of 6 to 10 days. Bicalutamide undergoes stereospecihc metabolism, where the S-enantiomer is cleared more rapidly by the liver than the -enantiomer. Nilutamide achieves peak serum concentrations between 1 to 4 hours after an oral dose and has a terminal half-life of 38 to 60 hours. Nilutamide is metabolized extensively, with less than 2% excreted as unchanged drug by the kidney. Side effects common to these agents are hot flashes, gynecomastia, and decreased libido. Flutamide tends to be associated with more diarrhea and requires three-times-daily administration, whereas bicalutamide is dosed once daily. Nilutamide may cause interstitial pneumonia and is associated with the visual disturbance of delayed adaptation to darkness. 

The effect of adding finasteride 5 mg/day to high-dose bicalutamide 150 mg/ day has been studied in 41 men with advanced prostate cancer treated over a mean of 3.9 years (21). The serum prostate-specific antigen (PSA) concentration was measured every 2 weeks until disease progression. At the first nadir of PSA, the median fall from baseline was 96.5% a second nadir occurred in 30 of 41 patients, with a median fall of 98.5% from baseline. The median times to each nadir were 3.7 and 5.8 weeks respectively. The median time to treatment failure was 21 months. Adverse effects were minor, including gynecomastia. Sex drive was normal in 17 of 29 men at baseline and in 12 of 24 men at the second PSA nadir, but one-third of the men had spontaneous erections at both times. The authors concluded that finasteride provided additional intracellular androgen blockade when added to bicalutamide. The duration of control was comparable to that achieved with castration, with preserved sexual function in some patients. 

Modalities to prevent priapism are limited and not well studied. Pseudoephedrine (30 or 60 mg/day given orally at bedtime) and leuprolide, a gonadotropin-releasing hormone, have been used to decrease the number of recurrent episodes of priapism. Hydroxyurea therapy may also be useful. Recently, low-doses of an antiandrogen, bicalutamide, have been used in two patients with SCD and one patient with spinal cord injury for treatment of recurrent and refractory priapism without major side effects. " " ... 

Bicalutamide is a chiral nonsteroidal antiandrogen used in the treatment of prostate cancer. Pharmacological activity resides mostly with the R enantiomer. The drug displays marked stereoselectivity in plasma concentrations, with much faster clearance of the S form in plasma (Table 1) [243]. The R S ratios of AUC after oral doses of 50 mg ranged from 74 to 290 in healthy subjects, and 97 to 290 in patients with hepatic impairment. The terminal ty is several days for the R enantiomer versus 6 to 37 hours for the S enantiomer [243]. 

---