Details
Stereochemistry | ACHIRAL |
Molecular Formula | C21H16F4N4O2S |
Molecular Weight | 464.436 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CNC(=O)C1=CC=C(C=C1F)N2C(=S)N(C(=O)C2(C)C)C3=CC(=C(C=C3)C#N)C(F)(F)F
InChI
InChIKey=WXCXUHSOUPDCQV-UHFFFAOYSA-N
InChI=1S/C21H16F4N4O2S/c1-20(2)18(31)28(12-5-4-11(10-26)15(8-12)21(23,24)25)19(32)29(20)13-6-7-14(16(22)9-13)17(30)27-3/h4-9H,1-3H3,(H,27,30)
Molecular Formula | C21H16F4N4O2S |
Molecular Weight | 464.436 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Enzalutamide (brand name Xtandi) is an orally bioavailable, organic, non-steroidal small molecule targeting the androgen receptor (AR) with potential antineoplastic activity. It was developed at UCLA and marketed by the pharmaceutical company Medivation for the treatment of metastatic castration-resistant prostate cancer. Through a mechanism that is reported to be different from other approved AR antagonists, enzalutamide inhibits the activity of prostate cancer cell ARs, which may result in a reduction in prostate cancer cell proliferation and, correspondingly, a reduction in the serum prostate specific antigen (PSA) level. AR over-expression in prostate cancer represents a key mechanism associated with prostate cancer hormone resistance.
CNS Activity
Curator's Comment: Enzalutamide crosses the blood–brain barrier and apparently leads to sensitization to seizures in small numbers of patients. The ability to cross the blood–brain barrier may be a therapeutic advantage in patients with advanced epidural or meningeal disease but calls for caution.
Originator
Sources: http://www.latimes.com/business/la-fi-pfizer-medivation-acquisition-20160822-snap-story.html
Curator's Comment: Medivation Inc., a San Francisco biotech company that sells a high-priced prostate cancer medication discovered by UCLA.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1871 |
21.4 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | XTANDI Approved UseIndicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). Launch Date2012 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.4 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25917876 |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
ENZALUTAMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
340 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25917876 |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
ENZALUTAMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6 day EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25917876 |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
ENZALUTAMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.94% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25917876 |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
ENZALUTAMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED |
Doses
Dose | Population | Adverse events |
---|---|---|
300 mg 2 times / day multiple, oral Highest studied dose Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: |
unhealthy, 68 years (range: 44–93 years ) n = 3 Health Status: unhealthy Condition: castration-resistant prostate cancer Age Group: 68 years (range: 44–93 years ) Sex: M Population Size: 3 Sources: |
DLT: Rash... Dose limiting toxicities: Rash (33%) Sources: |
300 mg 2 times / day multiple, oral Highest studied dose Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: |
unhealthy, 68 years (range: 44–93 years ) n = 3 Health Status: unhealthy Condition: castration-resistant prostate cancer Age Group: 68 years (range: 44–93 years ) Sex: M Population Size: 3 Sources: |
DLT: Seizure... Dose limiting toxicities: Seizure (33%) Sources: |
300 mg 2 times / day multiple, oral Highest studied dose Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: |
unhealthy, 68 years (range: 44–93 years ) n = 3 Health Status: unhealthy Condition: castration-resistant prostate cancer Age Group: 68 years (range: 44–93 years ) Sex: M Population Size: 3 Sources: |
Other AEs: Convulsions... |
240 mg 1 times / day multiple, oral MTD Dose: 240 mg, 1 times / day Route: oral Route: multiple Dose: 240 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 44–93 years ) n = 29 Health Status: unhealthy Condition: castration-resistant prostate cancer Age Group: 68 years (range: 44–93 years ) Sex: M Population Size: 29 Sources: |
Disc. AE: Fatigue... Other AEs: Fatigue... AEs leading to discontinuation/dose reduction: Fatigue (3%) Other AEs:Fatigue (grade 3-4, 17%) Sources: |
240 mg 2 times / day multiple, oral Dose: 240 mg, 2 times / day Route: oral Route: multiple Dose: 240 mg, 2 times / day Sources: |
unhealthy, 68 years (range: 44–93 years ) n = 22 Health Status: unhealthy Condition: castration-resistant prostate cancer Age Group: 68 years (range: 44–93 years ) Sex: M Population Size: 22 Sources: |
DLT: Seizure... Dose limiting toxicities: Seizure (5%) Sources: |
360 mg 1 times / day multiple, oral Dose: 360 mg, 1 times / day Route: oral Route: multiple Dose: 360 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 44–93 years ) n = 28 Health Status: unhealthy Condition: castration-resistant prostate cancer Age Group: 68 years (range: 44–93 years ) Sex: M Population Size: 28 Sources: |
DLT: Seizure... Dose limiting toxicities: Seizure (4%) Sources: |
160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Disc. AE: Seizure, Infection... Other AEs: Asthenia, Asthenia... AEs leading to discontinuation/dose reduction: Seizure (0.9%) Other AEs:Infection (grade 5, 1%) Sepsis (grade 5, 1%) Asthenia (grade 1-4, 50.6%) Sources: Asthenia (grade 3-4, 9%) Fatigue (grade 1-4, 50.6%) Fatigue (grade 3-4, 9%) Peripheral edema (grade 1-4, 15.4%) Peripheral edema (grade 3-4, 1%) Back pain (grade 1-4, 26.4%) Back pain (grade 3-4, 5.3%) Arthralgia (grade 1-4, 20.5%) Arthralgia (grade 3-4, 2.5%) Musculoskeletal pain (grade 1-4, 15%) Musculoskeletal pain (grade 3-4, 1.3%) Muscular weakness (grade 1-4, 9.8%) Muscular weakness (grade 3-4, 1.5%) Musculoskeletal stiffness (grade 1-4, 2.6%) Musculoskeletal stiffness (grade 3-4, 0.3%) Diarrhea (grade 1-4, 21.8%) Diarrhea (grade 3-4, 1.1%) Hot flush (grade 1-4, 20.3%) Hypertension (grade 1-4, 6.4%) Hypertension (grade 3-4, 2.1%) Headache (grade 1-4, 12.1%) Headache (grade 3-4, 0.9%) Dizziness (grade 1-4, 9.5%) Dizziness (grade 3-4, 0.5%) Vertigo (grade 1-4, 9.5%) Vertigo (grade 3-4, 0.5%) Cauda equina syndrome (grade 1-4, 7.4%) Cauda equina syndrome (grade 3-4, 6.6%) Paresthesia (grade 1-4, 6.6%) Amnesia (grade 1-4, 4.3%) Memory impairment (grade 1-4, 4.3%) Cognitive disorder (grade 1-4, 4.3%) Disturbance in attention (grade 1-4, 4.3%) Amnesia (grade 3-4, 0.3%) Memory impairment (grade 3-4, 0.3%) Cognitive disorder (grade 3-4, 0.3%) Disturbance in attention (grade 3-4, 0.3%) Hypoesthesia (grade 1-4, 4%) Hypoesthesia (grade 3-4, 0.3%) Nasopharyngitis (grade 1-4, 10.9%) Upper respiratory tract infection (grade 1-4, 10.9%) Sinusitis (grade 1-4, 10.9%) Rhinitis (grade 1-4, 10.9%) Pharyngitis (grade 1-4, 10.9%) Laryngitis (grade 1-4, 10.9%) Pneumonia (grade 1-4, 8.5%) Lower respiratory tract infection (grade 1-4, 8.5%) Bronchitis (grade 1-4, 8.5%) Lung infection (grade 1-4, 8.5%) Pneumonia (grade 3-4, 2.4%) Lower respiratory tract infection (grade 3-4, 2.4%) Bronchitis (grade 3-4, 2.4%) Lung infection (grade 3-4, 2.4%) Insomnia (grade 1-4, 8.8%) Anxiety (grade 1-4, 6.5%) Anxiety (grade 3-4, 0.3%) Hematuria (grade 1-4, 6.9%) Hematuria (grade 3-4, 1.8%) Pollakiuria (grade 1-4, 4.8%) Fall (grade 1-4, 4.6%) Fall (grade 3-4, 0.3%) Pruritus (grade 1-4, 3.8%) Dry skin (grade 1-4, 3.5%) Epistaxis (grade 1-4, 3.3%) Epistaxis (grade 3-4, 0.1%) Neutropenia (grade 1-4, 15%) Bilirubin increased (grade 1-4, 3%) |
160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: Page: p. 79 |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: Page: p. 79 |
Disc. AE: Thrombocytopenia, Colonic obstruction... AEs leading to discontinuation/dose reduction: Thrombocytopenia (0.2%) Sources: Page: p. 79Colonic obstruction (0.2%) Diarrhea (0.2%) Fatigue (0.6%) Rash (0.2%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Rash | 33% DLT, Disc. AE |
300 mg 2 times / day multiple, oral Highest studied dose Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: |
unhealthy, 68 years (range: 44–93 years ) n = 3 Health Status: unhealthy Condition: castration-resistant prostate cancer Age Group: 68 years (range: 44–93 years ) Sex: M Population Size: 3 Sources: |
Seizure | 33% DLT, Disc. AE |
300 mg 2 times / day multiple, oral Highest studied dose Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: |
unhealthy, 68 years (range: 44–93 years ) n = 3 Health Status: unhealthy Condition: castration-resistant prostate cancer Age Group: 68 years (range: 44–93 years ) Sex: M Population Size: 3 Sources: |
Convulsions | grade 3-4, 33% | 300 mg 2 times / day multiple, oral Highest studied dose Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: |
unhealthy, 68 years (range: 44–93 years ) n = 3 Health Status: unhealthy Condition: castration-resistant prostate cancer Age Group: 68 years (range: 44–93 years ) Sex: M Population Size: 3 Sources: |
Fatigue | 3% Disc. AE |
240 mg 1 times / day multiple, oral MTD Dose: 240 mg, 1 times / day Route: oral Route: multiple Dose: 240 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 44–93 years ) n = 29 Health Status: unhealthy Condition: castration-resistant prostate cancer Age Group: 68 years (range: 44–93 years ) Sex: M Population Size: 29 Sources: |
Fatigue | grade 3-4, 17% | 240 mg 1 times / day multiple, oral MTD Dose: 240 mg, 1 times / day Route: oral Route: multiple Dose: 240 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 44–93 years ) n = 29 Health Status: unhealthy Condition: castration-resistant prostate cancer Age Group: 68 years (range: 44–93 years ) Sex: M Population Size: 29 Sources: |
Seizure | 5% DLT, Disc. AE |
240 mg 2 times / day multiple, oral Dose: 240 mg, 2 times / day Route: oral Route: multiple Dose: 240 mg, 2 times / day Sources: |
unhealthy, 68 years (range: 44–93 years ) n = 22 Health Status: unhealthy Condition: castration-resistant prostate cancer Age Group: 68 years (range: 44–93 years ) Sex: M Population Size: 22 Sources: |
Seizure | 4% DLT, Disc. AE |
360 mg 1 times / day multiple, oral Dose: 360 mg, 1 times / day Route: oral Route: multiple Dose: 360 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 44–93 years ) n = 28 Health Status: unhealthy Condition: castration-resistant prostate cancer Age Group: 68 years (range: 44–93 years ) Sex: M Population Size: 28 Sources: |
Seizure | 0.9% Disc. AE |
160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Laryngitis | grade 1-4, 10.9% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Nasopharyngitis | grade 1-4, 10.9% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Pharyngitis | grade 1-4, 10.9% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Rhinitis | grade 1-4, 10.9% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Sinusitis | grade 1-4, 10.9% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Upper respiratory tract infection | grade 1-4, 10.9% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Headache | grade 1-4, 12.1% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Musculoskeletal pain | grade 1-4, 15% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Neutropenia | grade 1-4, 15% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Peripheral edema | grade 1-4, 15.4% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Musculoskeletal stiffness | grade 1-4, 2.6% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Hot flush | grade 1-4, 20.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Arthralgia | grade 1-4, 20.5% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Diarrhea | grade 1-4, 21.8% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Back pain | grade 1-4, 26.4% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Bilirubin increased | grade 1-4, 3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Epistaxis | grade 1-4, 3.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Dry skin | grade 1-4, 3.5% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Pruritus | grade 1-4, 3.8% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Hypoesthesia | grade 1-4, 4% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Amnesia | grade 1-4, 4.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Cognitive disorder | grade 1-4, 4.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Disturbance in attention | grade 1-4, 4.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Memory impairment | grade 1-4, 4.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Fall | grade 1-4, 4.6% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Pollakiuria | grade 1-4, 4.8% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Asthenia | grade 1-4, 50.6% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Fatigue | grade 1-4, 50.6% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Hypertension | grade 1-4, 6.4% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Anxiety | grade 1-4, 6.5% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Paresthesia | grade 1-4, 6.6% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Hematuria | grade 1-4, 6.9% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Cauda equina syndrome | grade 1-4, 7.4% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Bronchitis | grade 1-4, 8.5% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Lower respiratory tract infection | grade 1-4, 8.5% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Lung infection | grade 1-4, 8.5% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Pneumonia | grade 1-4, 8.5% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Insomnia | grade 1-4, 8.8% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Dizziness | grade 1-4, 9.5% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Vertigo | grade 1-4, 9.5% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Muscular weakness | grade 1-4, 9.8% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Epistaxis | grade 3-4, 0.1% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Amnesia | grade 3-4, 0.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Anxiety | grade 3-4, 0.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Cognitive disorder | grade 3-4, 0.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Disturbance in attention | grade 3-4, 0.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Fall | grade 3-4, 0.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Hypoesthesia | grade 3-4, 0.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Memory impairment | grade 3-4, 0.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Musculoskeletal stiffness | grade 3-4, 0.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Dizziness | grade 3-4, 0.5% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Vertigo | grade 3-4, 0.5% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Headache | grade 3-4, 0.9% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Peripheral edema | grade 3-4, 1% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Diarrhea | grade 3-4, 1.1% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Musculoskeletal pain | grade 3-4, 1.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Muscular weakness | grade 3-4, 1.5% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Hematuria | grade 3-4, 1.8% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Hypertension | grade 3-4, 2.1% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Bronchitis | grade 3-4, 2.4% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Lower respiratory tract infection | grade 3-4, 2.4% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Lung infection | grade 3-4, 2.4% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Pneumonia | grade 3-4, 2.4% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Arthralgia | grade 3-4, 2.5% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Back pain | grade 3-4, 5.3% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Cauda equina syndrome | grade 3-4, 6.6% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Asthenia | grade 3-4, 9% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Fatigue | grade 3-4, 9% | 160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Infection | grade 5, 1% Disc. AE |
160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Sepsis | grade 5, 1% Disc. AE |
160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: |
Colonic obstruction | 0.2% Disc. AE |
160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: Page: p. 79 |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: Page: p. 79 |
Diarrhea | 0.2% Disc. AE |
160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: Page: p. 79 |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: Page: p. 79 |
Rash | 0.2% Disc. AE |
160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: Page: p. 79 |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: Page: p. 79 |
Thrombocytopenia | 0.2% Disc. AE |
160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: Page: p. 79 |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: Page: p. 79 |
Fatigue | 0.6% Disc. AE |
160 mg 1 times / day steady, oral Recommended Dose: 160 mg, 1 times / day Route: oral Route: steady Dose: 160 mg, 1 times / day Sources: Page: p. 79 |
unhealthy, 69 years (range: 41-92 years) n = 800 Health Status: unhealthy Condition: metastatic castration-resistant prostate cancer Age Group: 69 years (range: 41-92 years) Sex: M Population Size: 800 Sources: Page: p. 79 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203415Orig1s000ClinPharmR.pdf#page=4 Page: 4.0 |
moderate | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203415Orig1s000ClinPharmR.pdf#page=4 Page: 4.0 |
moderate | |||
Page: - |
strong | yes (co-administration study) Comment: Co-administration of a strong CYP3A4 inhibitor (itraconazole) increased the composite AUC of enzalutamide plus Ndesmethyl enzalutamide by 1.3 fold in healthy volunteers Page: - |
||
yes [IC50 1.67 uM] | ||||
yes [IC50 10 uM] | no (co-administration study) Comment: Among these enzymes, the IC50 of CYP2C8 was the lowest. However, enzalutamide at steady state did not cause a clinically relevant change in the AUC of pioglitazone (CYP2C8 substrate) in vivo. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203415Orig1s000ClinPharmR.pdf#page=4 Page: 4.0 |
|||
yes [IC50 23 uM] | ||||
yes [IC50 42 uM] | ||||
yes [IC50 50 uM] | ||||
yes [IC50 56 uM] | ||||
yes | ||||
yes | ||||
Page: - |
yes | yes (co-administration study) Comment: Co-administration of a strong CYP2C8 inhibitor (gemfibrozil) increased the composite area under the plasmaconcentration-time curve (AUC) of enzalutamide plus N-desmethyl enzalutamide in healthy volunteers. Page: - |
Drug as victim
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203415Orig1s000PharmR.pdf#page=44 Page: 44.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Development of a second-generation antiandrogen for treatment of advanced prostate cancer. | 2009 May 8 |
|
Discovery of aryloxy tetramethylcyclobutanes as novel androgen receptor antagonists. | 2011 Nov 10 |
|
Inhibitors of androgen receptor activation function-2 (AF2) site identified through virtual screening. | 2011 Sep 22 |
|
Androgen receptor promotes ligand-independent prostate cancer progression through c-Myc upregulation. | 2013 |
|
NF-κB2/p52 induces resistance to enzalutamide in prostate cancer: role of androgen receptor and its variants. | 2013 Aug |
|
Enzalutamide in metastatic prostate cancer before chemotherapy. | 2014 Jul 31 |
|
Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. | 2014 Jun 12 |
|
Molecular alterations and emerging targets in castration resistant prostate cancer. | 2014 Mar |
|
Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies. | 2015 Jul 13 |
|
LncRNA HOTAIR Enhances the Androgen-Receptor-Mediated Transcriptional Program and Drives Castration-Resistant Prostate Cancer. | 2015 Oct 6 |
Sample Use Guides
160 mg (four 40 mg capsules) administered orally once daily
Route of Administration:
Oral
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=24662833
Resistant cells were maintained in vitro under constant exposure to 10 μM of enzalutamide.
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 16:30:25 GMT 2023
by
admin
on
Fri Dec 15 16:30:25 GMT 2023
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Record UNII |
93T0T9GKNU
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Record Status |
Validated (UNII)
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C146993
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NDF-RT |
N0000175560
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LIVERTOX |
NBK548070
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WHO-ATC |
L02BB04
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Code System | Code | Type | Description | ||
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6812
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15951529
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Enzalutamide
Created by
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DTXSID10912307
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93T0T9GKNU
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100000138095
Created by
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93T0T9GKNU
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PRIMARY | |||
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N0000185507
Created by
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PRIMARY | Cytochrome P450 2C9 Inducers [MoA] | ||
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CHEMBL1082407
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DB08899
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9621
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4628
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68534
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C540278
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SUB77412
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915087-33-1
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1307298
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N0000185607
Created by
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PRIMARY | Cytochrome P450 2C19 Inducers [MoA] | ||
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N0000185506
Created by
admin on Fri Dec 15 16:30:25 GMT 2023 , Edited by admin on Fri Dec 15 16:30:25 GMT 2023
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PRIMARY | Cytochrome P450 3A4 Inducers [MoA] | ||
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C71744
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PRIMARY | |||
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m11683
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PRIMARY |
Related Record | Type | Details | ||
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METABOLIC ENZYME -> INDUCER |
Therefore, co-administration of enzalutamide with CYP3A4, 2C9, and 2C19 substrates with a narrow therapeutic index should be avoided.
MODERATE
|
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|
TARGET -> INHIBITOR RESISTANT | |||
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TRANSPORTER -> INHIBITOR | |||
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METABOLIC ENZYME -> INHIBITOR | |||
|
LABELED -> NON-LABELED |
|
||
|
METABOLIC ENZYME -> INHIBITOR | |||
|
TARGET -> AGONIST |
BINDING
|
||
|
METABOLIC ENZYME -> SUBSTRATE |
In vivo, the sum of enzalutamide and M2 exposure was increased by 2.2-fold and 1.3-fold when it was co-administered with gemfibrozil (strong CYP2C8 inhibitor) or itraconazole (strong CYP3A4 inhibitor), respectively.
|
||
|
METABOLIC ENZYME -> INHIBITOR | |||
|
BINDER->LIGAND |
BINDING
|
||
|
METABOLIC ENZYME -> INHIBITOR | |||
|
METABOLIC ENZYME -> INHIBITOR | |||
|
METABOLIC ENZYME -> INHIBITOR | |||
|
METABOLIC ENZYME -> SUBSTRATE |
In vivo, the sum of enzalutamide and M2 exposure was increased by 2.2-fold and 1.3-fold when it was co-administered with gemfibrozil (strong CYP2C8 inhibitor) or itraconazole (strong CYP3A4 inhibitor), respectively. If the co-administration of enzalutamide with a strong CYP2C8 inhibitor cannot be avoided, the daily enzalutamide dose should be reduced to 80 mg.
|
||
|
METABOLIC ENZYME -> INHIBITOR |
TIME-DEPENDENT INHIBITION
|
||
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TARGET -> AGONIST | |||
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TARGET -> INHIBITOR | |||
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METABOLIC ENZYME -> INDUCER |
Therefore, co-administration of enzalutamide with CYP3A4, 2C9, and 2C19 substrates with a narrow therapeutic index should be avoided.
MODERATE
|
||
|
METABOLIC ENZYME -> INDUCER |
Therefore, co-administration of enzalutamide with CYP3A4, 2C9, and 2C19 substrates with a narrow therapeutic index should be avoided
STRONG
|
||
|
METABOLIC ENZYME -> INHIBITOR |
Related Record | Type | Details | ||
---|---|---|---|---|
|
METABOLITE -> PARENT |
MINOR
URINE
|
||
|
METABOLITE INACTIVE -> PARENT |
In plasma, M1 accounted for 10% of the 14C-radioactivity. In urine, the most abundant 14C-component was M1 (62.7% of dose). In feces, the most abundant 14C-components were M1 and M10, which accounted for 3.34% and 4.26% of the radioactive dose, respectively.
FECAL; PLASMA; URINE
|
||
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METABOLITE -> PARENT |
In urine, M10 was a minor metabolite, which accounted for 0.67% of the dose. In feces, M10 was one of the most abundant 14C-components, and it accounted for 4.26% of the radioactive dose.
FECAL; URINE
|
||
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METABOLITE -> PARENT |
Metabolite M7 was trace component in plasma; accounting for ≤ 2% of the radioactivity in the 6- and 24-hour postdose plasma samples and not detected at any other time point. In urine, M7 accounted for 9.45% of the radioactive dose. In feces, M7 accounted for 1.12% of the radioactive dose.
FECAL; PLASMA; URINE
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METABOLITE -> PARENT |
Trace amount of M6 was observed in urine (≤ 0.42% of the dose) and plasma (≤ 2% of the radioactivity in the 6- and 24-hour postdose plasma samples and not detected at any other time point).
MINOR
PLASMA; URINE
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IMPURITY -> PARENT |
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IMPURITY -> PARENT |
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IMPURITY -> PARENT |
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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SINGLE ORAL DOSE |
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Tmax | PHARMACOKINETIC |
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DOSE |
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Volume of Distribution | PHARMACOKINETIC |
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