Metabolic/Endocrine: Decreased glucose tolerance (see PRECAUTIONS ), increased serum levels of low-density lipoproteins and decreased levels of high-density lipoproteins (see PRECAUTIONS , Laboratory Tests ), increased creatine and creatinine excretion, increased serum levels of creatinine phosphokinase (CPK). Reversible changes in liver function tests also occur, including increased Bromsulphalein (BSP) retention and increases in serum bilirubin , glutamic-oxaloacetic transaminase ( SGOT ), and alkaline phosphatase .
Flutamide acts as a selective, competitive , silent antagonist of the androgen receptor (AR).  Its active metabolite , 2-hydroxyflutamide , has between 10- to 25-fold higher affinity for the AR than does flutamide, and hence is a more powerful antiandrogen in comparison.     However, at high concentrations, unlike flutamide, 2-hydroxyflutamide is able to weakly activate the AR.   Flutamide has far lower affinity for the AR than do steroidal antiandrogens like spironolactone and cyproterone acetate, and it is a relatively weak antiandrogen in terms of potency by weight, but the large dosages at which flutamide is used appear to compensate for this.  In accordance with its selectivity for the AR, flutamide possesses no progestogenic , (direct) estrogenic , glucocorticoid , or antigonadotropic activity.   Similarly to nilutamide, bicalutamide, and enzalutamide , flutamide crosses the blood-brain-barrier and exerts central antiandrogen actions. 
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