In human hepatic venous bodies, nilutamide (110 μM) inhibits the enzymes hexabarbitic cardiovascular demethylase, amphetamine N-demethylase, benzo(a)pyrene venase, and 7-ethylaniline coumarin, in that order. 85%, 40%, 35%, and 25% of the protein O-determinase activity is reported[2]. Nilumid (550 μM) does not modify the kinetics of NADPH-cytochrome P-450 reductase in reducing cytochrome P-450 in NADPH anaerobic systems, nor does it significantly increase the consumption of NADPH by microparticulate oxygen [2]. In nilutamide burst T-47D cells and ZR-75-1 cells, GCDFP-15 release produced by 1 nM testosterone was dramatically elevated, with IC50 values of 87 nM and 75 nM, respectively [3].

Animal/Disease Models: Female NMRI mice (20-22 g; n=165; infected with approximately 80 Schistosoma mansoni cercariae injected subcutaneously (sc) (sc)) [4]
Doses: 50, 100, 200 and 400 mg/kg
Route of Administration: po (po (oral gavage)) Single dose (21- or 49-day-old S. mansoni infection)
Experimental Results: Total larval load was diminished by 11.0%, 5.1%, 21.9% and 35.6% at doses of 50, 100, 200 and 400 mg/kg, respectively. Female larvae were diminished by 27.5%, 26.1%, 75.4% and 22.5% respectively at doses of 50, 100, 200 and 400 mg/kg. A moderate reduction of 30.7%-49.6% in adult worms was observed at doses of 100 and 200 mg/kg. At the dose of 400 mg/kg, the total adult worm burden and female adult worm burden were diminished by 84.8% and 71.3% respectively.

Absorption, Distribution and Excretion
Rapidly and completely absorbed, yielding high and persistent plasma concentrations.
Nilutamide is extensively metabolized andless than 2% of the drug is excreted unchanged in urine after 5 days. Fecal elimination is negligible, ranging from 1.4% to 7% of the dose after 4 to 5 days.

---

Metabolism / Metabolites
The results of a human metabolism study using 14C-radiolabelled tablets show that nilutamide is extensively metabolized and less than 2% of the drug is excreted unchanged in urine after 5 days.
The results of a human metabolism study using 14C-radiolabelled tablets show that nilutamide is extensively metabolized and less than 2% of the drug is excreted unchanged in urine after 5 days.
Route of Elimination: Nilutamide is extensively metabolized andless than 2% of the drug is excreted unchanged in urine after 5 days. Fecal elimination is negligible, ranging from 1.4% to 7% of the dose after 4 to 5 days.
Half Life: 38.0-59.1 hours

---

Biological Half-Life
38.0-59.1 hours

Toxicity Summary
Nilutamide competes with androgen for the binding of androgen receptors, consequently blocking the action of androgens of adrenal and testicular origin that stimulate the growth of normal and malignant prostatic tissue. This blockade of androgen receptors may result in growth arrest or transient tumor regression through inhibition of androgen-dependent DNA and protein synthesis.

---

Hepatotoxicity
In large registration clinical trials, ALT elevations occurred in 8% (range 2% to 33%) of patients during nilutamide therapy. The elevations were usually mild, asymptomatic and transient, requiring drug discontinuation in only 1% of treated patients. In rare instances, clinically apparent acute liver injury has occurred during nilutamide therapy, but the number of published cases are few, and the agent appears to be less hepatotoxic than flutamide. Nevertheless, fatal cases have been reported (Case 1). In reported cases, the latency to onset averaged 2 to 4 months and the clinical pattern of enzyme elevations was typically hepatocellular, thus largely resembling flutamide induced liver injury. Signs of hypersensitivity and autoimmunity were not common.
Likelihood score: C (probable cause of clinically apparent liver injury).

[1]. Nilutamide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in prostate cancer. Drugs Aging. 1993 Jan-Feb;3(1):9-25.

[2]. Inhibitory effects of nilutamide, a new androgen receptor antagonist, on mouse and human liver cytochrome P-450. Biochem Pharmacol. 1989 Mar 15;38(6):941-7.

[3]. Comparison of in vitro effects of the pure antiandrogens OH-flutamide, Casodex, and nilutamide on androgen-sensitive parameters. Urology. 1997 Apr;49(4):580-6; discussion 586-9.

[4]. Keiser J, Vargas M, Vennerstrom JL. Activity of antiandrogens against juvenile and adult Schistosoma mansoni in mice. J Antimicrob Chemother. 2010 Sep;65(9):1991-5.

Nilutamide is an imidazolidinone, a member of (trifluoromethyl)benzenes and a C-nitro compound. It has a role as an antineoplastic agent and an androgen antagonist.
Nilutamide is an antineoplastic hormonal agent primarily used in the treatment of prostate cancer. Nilutamide is a pure, nonsteroidal anti-androgen with affinity for androgen receptors (but not for progestogen, estrogen, or glucocorticoid receptors). Consequently, Nilutamide blocks the action of androgens of adrenal and testicular origin that stimulate the growth of normal and malignant prostatic tissue. Prostate cancer is mostly androgen-dependent and can be treated with surgical or chemical castration. To date, antiandrogen monotherapy has not consistently been shown to be equivalent to castration.
Nilutamide is an Androgen Receptor Inhibitor. The mechanism of action of nilutamide is as an Androgen Receptor Antagonist.
Nilutamide is a first generation, oral nonsteroidal antiandrogen similar in structure to flutamide that is used in the therapy of prostate cancer. Nilutamide is associated with a low rate of serum aminotransferase elevations during therapy and with rare instances of clinically apparent, acute liver injury.
Nilutamide is a synthetic, nonsteroidal agent with antiandrogenic properties. Nilutamide preferentially binds to androgen receptors and blocks androgen receptor activation by testosterone and other androgens; this agent may inhibit androgen-dependent growth of normal and neoplastic prostate cells. (NCI04)
Nilutamide is an antineoplastic hormonal agent primarily used in the treatment of prostate cancer. Nilutamide is a pure, nonsteroidal anti-androgen with affinity for androgen receptors (but not for progestogen, estrogen, or glucocorticoid receptors). Consequently, Nilutamide blocks the action of androgens of adrenal and testicular origin that stimulate the growth of normal and malignant prostatic tissue. Prostate cancer is mostly androgen-dependent and can be treated with surgical or chemical castration. To date, antiandrogen monotherapy has not consistently been shown to be equivalent to castration.

---

Drug Indication
For use in combination with surgical castration for the treatment of metastatic prostate cancer involving distant lymph nodes, bone, or visceral organs (Stage D2).
FDA Label

---

Mechanism of Action
Nilutamide competes with androgen for the binding of androgen receptors, consequently blocking the action of androgens of adrenal and testicular origin that stimulate the growth of normal and malignant prostatic tissue. This blockade of androgen receptors may result in growth arrest or transient tumor regression through inhibition of androgen-dependent DNA and protein synthesis.

---

Pharmacodynamics
Nilutamide is an antineoplastic hormonal agent primarily used in the treatment of prostate cancer. Nilutamide is a pure, nonsteroidal anti-androgen with affinity for androgen receptors (but not for progestogen, estrogen, or glucocorticoid receptors). Consequently, Nilutamide blocks the action of androgens of adrenal and testicular origin that stimulate the growth of normal and malignant prostatic tissue. Prostate cancer is mostly androgen-dependent and can be treated with surgical or chemical castration. To date, antiandrogen monotherapy has not consistently been shown to be equivalent to castration. The relative binding affinity of nilutamide at the androgen receptor is less than that of bicalutamide, but similar to that of hydroxuflutamide.

C12H10F3N3O4

317.2207

317.062

63612-50-0

Nilutamide-d6;1189477-66-4

4493

Light yellow to yellow solid powder

1.5±0.1 g/cm3

1490C

1.524

2.23

1

7

1

22

515

0

XWXYUMMDTVBTOU-UHFFFAOYSA-N

InChI=1S/C12H10F3N3O4/c1-11(2)9(19)17(10(20)16-11)6-3-4-8(18(21)22)7(5-6)12(13,14)15/h3-5H,1-2H3,(H,16,20)

5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]imidazolidine-2,4-dione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 250 mg/mL (~788.10 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.08 mg/mL (6.56 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.08 mg/mL (6.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)