Flutamide, an antiandrogen drug, is widely used for the treatment of prostate cancer. The major metabolic pathways of flutamide are hydroxylation and hydrolysis. The hydrolyzed metabolite, 5-amino2-nitrobenzotrifluoride (FLU-1), is further metabolized to N-hydroxy FLU-1, an assumed hepatotoxicant. Our previous study demonstrated that arylacetamide deacetylase (AADAC), one of the major serine es...

Flutamide, a widely used nonsteroidal antiandrogen drug for the treatment of prostate cancer, has been associated with rare incidences of hepatotoxicity in patients. It is believed that bioactivation of flutamide and subsequent covalent binding to cellular proteins is responsible for its toxicity. A novel N-S glutathione adduct has been identified in a previous bioactivation study of flutamide ...

Flutamide, an androgen receptor antagonist, is thought to improve cardiovascular function by blocking the androgen receptor after trauma-hemorrhage (T-H). Although 17beta-estradiol (E2) and flutamide improve cardiac function after T-H, whether E2 and flutamide produce their salutary effect via the same or a different mechanism is unknown. We hypothesized that E2 and flutamide mediate their effe...

The role of androgen receptor (AR) mutations in androgen-independent prostate cancer (PCa) was determined by examining AR transcripts and genes from a large series of bone marrow metastases. Mutations were found in 5 of 16 patients who received combined androgen blockade with the AR antagonist flutamide, and these mutant ARs were strongly stimulated by flutamide. In contrast, the single mutant ...

Flutamide, a nonsteroidal antiandrogen drug widely used in the treatment of prostate cancer, has been associated with rare incidences of hepatotoxicity in patients. It is believed that bioactivation of flutamide and subsequent covalent binding to cellular proteins is responsible for its toxicity. Current in vitro studies were undertaken to probe the cytochrome P450 (P450)-mediated bioactivation...

BACKGROUND Flutamide is an antiandrogen devoid of other hormonal effects, except for a decrease in the secretion of adrenal androgens such as dehydroepidandrosterone sulphate (DHEA-s) and androstenedione. AIM To assess the effectiveness of flutamide in the treatment of hirsutism, used as monotherapy or combined with oral contraceptives (OC). PATIENTS AND METHODS Women with peripheral hirsut...

The androgen receptor antagonist, flutamide, is strongly associated with idiosyncratic drug-induced liver injury (DILI). Following administration, flutamide undergoes extensive first-pass metabolism to its primary metabolite, 2-hydroxyflutamide. Flutamide is a known mitochondrial toxicant; however there has been limited investigation into the potential mitochondrial toxicity of 2-hydroxyflutami...

HYPOTHESIS Flutamide, a testosterone receptor antagonist, produces various beneficial effects in male rats following hemorrhagic shock, possibly as a result of a direct vasodilating effect on large and small vessels in the rat. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES The aorta and the small intestine were isolated from normal male and female Sprague-Dawley rats. Isolated aortic rings...

BACKGROUND Combined androgen blockade for the treatment of metastatic prostate cancer consists of an antiandrogen drug plus castration. In a previous trial, we found that adding the antiandrogen flutamide to leuprolide acetate (a synthetic gonadotropin-releasing hormone that results in medical ablation of testicular function) significantly improved survival as compared with that achieved with p...

BACKGROUND It has previously been speculated that the androgen receptor antagonist flutamide produces behavioral effects that are not mediated by androgen receptors. These earlier studies were performed in intact rodents and thus, flutamide may have interfered with endogenous testosterone produced by the testes. The main objective of the present study was to examine whether flutamide induces an...