Flutamide 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. 

Gastrointestinal effects are common when flutamide is used to treat advanced cases of prostate cancer. At doses of 250 mg every 8 hours or 500 mg/day, 23 of 106 men had gastrointestinal problems, irrespective of the dosage regimen (45). There was no difference in the incidence of these effects in the 56 men who had previously received external beam radiation and 50 others who had undergone radical prostatectomy. This suggests that the gastrointestinal adverse effects of flutamide are not due to a local toxic effect. 

This is the first reported case of enterocolic lymphocytic phlebitis, a rare form of vasculitis, in conjunction with lymphocytic colitis, lymphocytic enteritis, and lymphocytic appendicitis. The fact that the patient was taking flutamide at the same time suggests that this peculiar form of lymphocytic inflammation of the veins and mucosa could represent a drug reaction. It should be recalled that diarrhea is a common complication of flutamide use, and perhaps occurs in severe degree in some 15% of men taking full-dose treatment. 

Column 5 Represents the dose (nM) that inhibits 50% (IC50) of the DHT-stimulated Shionogi mouse mammary carcinoma cell number. Lower values are preferable. Column 6 Represents a comparison of antiandrogenic efficacy (%) of selected experimental agents in rat prostate to that of flutamide (FLU). 

A 68-year-old man had a photosensitive drug eruption while taking flutamide (24). The minimal erjhhema dose with ultraviolet A light was reduced to 2 J/cm and recovered to over 16 J/cm after withdrawal, without changing reactivity to ultraviolet B. The absorption spectrum of flutamide was not altered after ultraviolet A irradiation. 

Flutamide is extensively and rapidly metaboli/cd. One hour after dosing, only 2.5% of the drug in plasma is unchanged. Tlie major metabolite in plasma is a-hydroxyflu-umidc however, the major metabolite found in urine is 2-amino-5-nitro-4-(trinuuromethyl)phenol. which results from cleavage of the side chain. 

A detrimental effect caused by androgens is also reported. Blockade of the endogenous testosterone by flutamide or depletion of testosterone (castration) improved myocardial function of the perfused rat hearts subjected to ischemia and reperfusion. This response was associated with decreased caspase l, caspase-3, caspase-11, decreased TNF-alpha, IL-1 beta, IL-6, decreased ischemia and reperfusion induced p38 MAPK activation and increased Bcl-2 expression in castrated and flutamide treated males.15 Accordingly, supraphysiological doses of nandrolone taken during exercise or under sedentary conditions increased myocardial susceptibility to ischemia and reperfusion injury in perfused rat hearts. Pre-ischemic c-AMP concentrations and pre-ischemic and reperfusion TNF-alpha concentrations were found to be increased in those hearts.16... 

Flutamide, a drug approved for treatment of prostate cancer, blocks the androgen receptor. It is used in combination with oral contraceptives in seborrhea and acne therapy for females. The dose is usually 250 to 500 mg twice daily over 6 months. 

Katchen B, Buxbaum S. Disposition of a new, nonsteroid, antiandrogen, alpha,alpha,al-pha-trifluoro-2-methyl-4 -nitro-m-propionotoluidide (Flutamide), in men following a single oral 200 mg dose. Journal of Clinical Endocrinology Metabolism 1975 41 373-379. 

Wang HS, Wang TH, Soong YK (1999) Low dose flutamide in the treatment of acne vulgaris in women with or without oligomenorrhea or amenorrhea. Changgeng Yi Xue Za Zhi 22 423-432... 

Castelo-Branco C, Del Pino M. Hepato-toxicity during low-dose flutamide treatment for hirsutism. Gynecol Endocrinol 2009 25 419-22. 

Bruni V, Peruzzi E, Dei M, Nanninl S, SeravalH V, Sisti G, et al. Hepatotoxicity with low- and ultralow-dose flutamide a surveillance study on 203 hyperandrogenic young females. Fertil Steril 2012 98(4) 1047-52. 

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