Identification

Summary

Enzalutamide is a second-generation androgen receptor inhibitor used to treat castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer.

Brand Names
Xtandi
Generic Name
Enzalutamide
DrugBank Accession Number
DB08899
Background

Enzalutamide is an androgen receptor (AR) inhibitor for the treatment of castration-resistant prostate cancer (CRPC), both metastatic and non-metastatic.8 It is a second-generation antiandrogen agent that the FDA approved on August 31, 2012.8,7 Although androgen deprivation therapy (ADT) is the first-line treatment of prostate cancer and remission can be achieved, arising resistance is inevitable, becoming castration-resistant prostate cancer.7 Until recently, docetaxel is the only treatment available for metastatic CRPC; however, AR inhibitors have been developed for more targeted therapy, although first-generation AR inhibitors like bicalutamide did not substantially increase the survival rate.7 Second-generation such as enzalutamide is more efficacious due to a higher affinity to AR and no partial agonist activity compared to bicalutamide.7,1

Due to a favorable pharmacological profile, a phase 1 study of enzalutamide was initiated in July 2007. Compared to the average time of 10 to 15 years for a drug to go from pre-clinical to clinical studies, enzalutamide was developed relatively rapidly.7

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 464.436
Monoisotopic: 464.093009286
Chemical Formula
C21H16F4N4O2S
Synonyms
  • Enzalutamida
  • Enzalutamide
External IDs
  • MDV 3100
  • MDV-3100
  • MDV3100

Pharmacology

Indication

Enzalutamide is indicated for the treatment of castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer.8

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Enzalutamide is a second-generation antiandrogen that blocks the activity of androgen and androgen receptor (AR) in prostate cancer. AR activity and prostate cancer progression are closely related due to the normal physiology of prostate cells, providing the rationale for androgen deprivation therapy (ADT).4 However, resistance will eventually arise after the commencement of ADT in 2-3 years due to the accumulation of mutations, including constitutively active mutation, AR overexpression, and changes in AR splicing variants.5,1 Enzalutamide was therefore designed to exploit these mutations.3 In vitro experiments in human prostate cancer cell line VCaP showed that enzalutamide can suppress cell growth and induce apoptosis while other antiandrogens like bicalutamide did not.3

Clinical trials on prostate cancer patients indicated that enzalutamide can lead to a decrease in serum PSA for at least 12 weeks, although this response can be short-lived and thus resulting in enzalutamide resistance.6,3 Patients receiving enzalutamide also had a 37% decreased in the risk of death compared to placebo.2

Mechanism of action

Enzalutamide is a competitive androgen receptor (AR) inhibitor that has a threefold inhibition on the androgen signaling pathway without significant AR agonist activity.9,1 It inhibits androgen binding to its receptor, androgen receptor nuclear translocation, and subsequent interaction with chromosomal DNA to upregulate oncogenes.1,2 Enzalutamide binds to the AR with 5 to 8-fold greater affinity than first-generation antiandrogens such as bicalutamide and only 2-3 fold reduced affinity than the natural ligand dihydrotestosterone.3 Molecular docking showed that enzalutamide binds to the ligand binding domain of the AR distinctive from that of bicalutamide.1

TargetActionsOrganism
AAndrogen receptor
inhibitor
Humans
Absorption

The median Tmax is 1 hour (0.5 to 3 hours) following a single 160 mg dose of capsules and 2 hours (0.5 to 6 hours) following a single 160 mg dose of tablets.9 Enzalutamide achieves steady-state by Day 28 and its AUC accumulates approximately 8.3-fold relative to a single dose. At steady-state, the mean (%CV) maximum concentration (Cmax) for enzalutamide and N-desmethyl enzalutamide is 16.6 µg/mL (23%) and 12.7 µg/mL (30%), respectively, and the mean (%CV) minimum concentrations (Cmin) are 11.4 µg/mL (26%) and 13.0 µg/mL (30%), respectively.9

Volume of distribution

The mean (%CV) volume of distribution after a single oral dose is 110 L (29%).9

Protein binding

Enzalutamide is 97% to 98% bound to plasma proteins, primarily albumin. N-desmethyl enzalutamide is 95% bound to plasma proteins.9

Metabolism

Enzalutamide is metabolized by CYP2C8 and CYP3A4. CYP2C8 is primarily responsible for the formation of the active metabolite (N-desmethyl enzalutamide). Carboxylesterase 1 metabolizes N-desmethyl enzalutamide and enzalutamide to the inactive carboxylic acid metabolite.9

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Route of elimination

Enzalutamide is primarily eliminated by hepatic metabolism. 71% of the dose is recovered in urine (including only trace amounts of enzalutamide and N-desmethyl enzalutamide), and 14% is recovered in feces (0.4% of the dose as unchanged enzalutamide and 1% as N-desmethyl enzalutamide).11

Half-life

The mean terminal half-life (t1/2) for enzalutamide in patients after a single oral dose is 5.8 days (range 2.8 to 10.2 days). Following a single 160 mg oral dose of enzalutamide in healthy volunteers, the mean terminal t1/2 for N-desmethyl enzalutamide is approximately 7.8 to 8.6 days.9

Clearance

The mean apparent clearance (CL/F) of enzalutamide after a single dose is 0.56 L/h (0.33 to 1.02 L/h).9

Adverse Effects
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Toxicity

In an embryo-fetal developmental toxicity study in mice, enzalutamide caused developmental toxicity when administered at oral doses of 10 or 30 mg/kg/day throughout the period of organogenesis (gestational days 6-15). Findings included embryo-fetal lethality (increased post-implantation loss and resorptions) and decreased anogenital distance at ≥ 10 mg/kg/day, and cleft palate and absent palatine bone at 30 mg/kg/day. Doses of 30 mg/kg/day caused maternal toxicity. The doses tested in mice (1, 10, and 30 mg/kg/day) resulted in systemic exposures (AUC) of approximately 0.04, 0.4, and 1.1 times, respectively, the exposures in patients. Enzalutamide did not cause developmental toxicity in rabbits when administered throughout the period of organogenesis (gestational days 6-18) at dose levels up to 10 mg/kg/day (approximately 0.4 times the exposures in patients based on AUC).9

In a pharmacokinetic study in pregnant rats with a single oral 30 mg/kg enzalutamide administration on gestation day 14, enzalutamide and/or its metabolites were present in the fetus at a Cmax that was approximately 0.3 times the concentration found in maternal plasma and occurred 4 hours after administration.9

Based on animal studies, XTANDI may impair fertility in males of reproductive potential. Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of XTANDI.9

The most common adverse reactions (≥ 5%) are asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension.9

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe serum concentration of 1,2-Benzodiazepine can be decreased when it is combined with Enzalutamide.
AbacavirAbacavir may decrease the excretion rate of Enzalutamide which could result in a higher serum level.
AbametapirThe serum concentration of Enzalutamide can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Enzalutamide can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be decreased when it is combined with Enzalutamide.
AbirateroneThe metabolism of Abiraterone can be increased when combined with Enzalutamide.
AbrocitinibThe serum concentration of Abrocitinib can be decreased when it is combined with Enzalutamide.
AcalabrutinibThe serum concentration of Acalabrutinib can be decreased when it is combined with Enzalutamide.
AceclofenacAceclofenac may decrease the excretion rate of Enzalutamide which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Enzalutamide which could result in a higher serum level.
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Food Interactions
  • Avoid St. John's Wort. This herb induces the CYP3A4 metabolism of enzalutamide and may reduce its serum concentration.
  • Take with or without food.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
XtandiCapsule40 mgOralAstellas Pharma Europe Bv2016-09-08Not applicableEU flag
XtandiCapsule40 mgOralAstellas Pharma Inc2013-06-07Not applicableCanada flag
XtandiCapsule40 mg/1OralAstellas Pharma US, Inc.2012-08-31Not applicableUS flag
XtandiTablet40 mg/1OralAstellas Pharma US, Inc.2020-08-04Not applicableUS flag
XtandiTablet80 mg/1OralAstellas Pharma US, Inc.2020-08-04Not applicableUS flag
XtandiTablet, film coated40 mgOralAstellas Pharma Europe Bv2020-12-16Not applicableEU flag
XtandiCapsule40 mg/1OralAstellas Pharma US, Inc.2012-08-31Not applicableUS flag
XtandiTablet40 mg/1OralAstellas Pharma US, Inc.2020-08-04Not applicableUS flag
XtandiTablet, film coated80 mgOralAstellas Pharma Europe Bv2020-12-16Not applicableEU flag

Categories

ATC Codes
L02BB04 — Enzalutamide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylimidazolidines. These are polycyclic compounds containing an imidazoline substituted by a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azolidines
Sub Class
Imidazolidines
Direct Parent
Phenylimidazolidines
Alternative Parents
Trifluoromethylbenzenes / 2-halobenzoic acids and derivatives / Alpha amino acids and derivatives / N-phenylthioureas / Benzamides / Benzoyl derivatives / Benzonitriles / Fluorobenzenes / Aryl fluorides / Imidazolidinones
show 11 more
Substituents
2-halobenzoic acid or derivatives / Alkyl fluoride / Alkyl halide / Alpha-amino acid or derivatives / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzamide / Benzenoid
show 29 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
benzamides, nitrile, imidazolidinone, monofluorobenzenes, (trifluoromethyl)benzenes, thiocarbonyl compound (CHEBI:68534)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
93T0T9GKNU
CAS number
915087-33-1
InChI Key
WXCXUHSOUPDCQV-UHFFFAOYSA-N
InChI
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)
IUPAC Name
4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl}-2-fluoro-N-methylbenzamide
SMILES
CNC(=O)C1=C(F)C=C(C=C1)N1C(=S)N(C(=O)C1(C)C)C1=CC=C(C#N)C(=C1)C(F)(F)F

References

General References
  1. Schalken J, Fitzpatrick JM: Enzalutamide: targeting the androgen signalling pathway in metastatic castration-resistant prostate cancer. BJU Int. 2016 Feb;117(2):215-25. doi: 10.1111/bju.13123. Epub 2015 Jun 6. [Article]
  2. Saad F: Evidence for the efficacy of enzalutamide in postchemotherapy metastatic castrate-resistant prostate cancer. Ther Adv Urol. 2013 Aug;5(4):201-10. doi: 10.1177/1756287213490054. [Article]
  3. Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL: Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009 May 8;324(5928):787-90. doi: 10.1126/science.1168175. Epub 2009 Apr 9. [Article]
  4. Heinlein CA, Chang C: Androgen receptor in prostate cancer. Endocr Rev. 2004 Apr;25(2):276-308. doi: 10.1210/er.2002-0032. [Article]
  5. Fujita K, Nonomura N: Role of Androgen Receptor in Prostate Cancer: A Review. World J Mens Health. 2019 Sep;37(3):288-295. doi: 10.5534/wjmh.180040. Epub 2018 Sep 10. [Article]
  6. Tan MH, Li J, Xu HE, Melcher K, Yong EL: Androgen receptor: structure, role in prostate cancer and drug discovery. Acta Pharmacol Sin. 2015 Jan;36(1):3-23. doi: 10.1038/aps.2014.18. Epub 2014 Jun 9. [Article]
  7. Menon MP, Higano CS: Enzalutamide, a second generation androgen receptor antagonist: development and clinical applications in prostate cancer. Curr Oncol Rep. 2013 Apr;15(2):69-75. doi: 10.1007/s11912-013-0293-9. [Article]
  8. FDA Approved Drug Products: Xtandi (enzalutamide) capsules/tablets for oral use [Link]
  9. FDA Approved Drug Products: Xtandi (enzalutamide) capsules/tablets for oral use 2022 [Link]
  10. Health Canada Approved Drug Products: Xtandi (enzalutamide) capsules/tablets for oral use 2022 [Link]
  11. Enzalutamide FDA label [Link]
Human Metabolome Database
HMDB0251831
KEGG Drug
D10218
PubChem Compound
15951529
PubChem Substance
175427141
ChemSpider
13093347
BindingDB
50425732
RxNav
1307298
ChEBI
68534
ChEMBL
CHEMBL1082407
ZINC
ZINC000034806477
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Enzalutamide
FDA label
Download (393 KB)
MSDS
Download (89.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentMetastatic Castration Resistant Prostate Cancer (CRPC)1
4CompletedTreatmentMetastatic Castration Resistant Prostate Cancer (CRPC)2
4CompletedTreatmentProstate Cancer2
4CompletedTreatmentRefractory, metastatic hormone-refractory Prostate cancer1
4RecruitingSupportive CareCastration Resistant Prostatic Cancer / Hormone Refractory Prostate Cancer / Recurrent Prostate Carcinoma / Refractory, metastatic hormone-refractory Prostate cancer / Stage IV Prostate Cancer1
4RecruitingTreatmentCastration Resistant Prostatic Neoplasms1
4RecruitingTreatmentMetastatic Castration Resistant Prostate Cancer (CRPC)1
4TerminatedTreatmentMetastatic Castration Resistant Prostate Cancer (CRPC)1
3Active Not RecruitingTreatmentAdenocarcinoma of the Prostate / Hormone Resistant Prostate Cancer / Prostate Cancer - Recurrent / Stage IV Prostate Cancer1
3Active Not RecruitingTreatmentCastration Resistant Prostatic Neoplasms1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral
CapsuleOral40 mg/1
TabletOral40 mg/1
TabletOral80 mg/1
Tablet, film coatedOral40 MG
Tablet, film coatedOral80 MG
Capsule, liquid filledOral40 mg
CapsuleOral40 mg
Capsule, liquid filledOral40.0 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8183274No2012-05-222026-05-15US flag
US9126941No2015-09-082026-05-15US flag
US7709517No2010-05-042027-08-13US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)201 ºCL43242
water solubilityInsoluble FDA label
logP3.0L43242
Predicted Properties
PropertyValueSource
Water Solubility0.00136 mg/mLALOGPS
logP3.75ALOGPS
logP4.16Chemaxon
logS-5.5ALOGPS
pKa (Strongest Acidic)13.05Chemaxon
pKa (Strongest Basic)-1.6Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area76.44 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity113.48 m3·mol-1Chemaxon
Polarizability42.69 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9356
Blood Brain Barrier+0.8514
Caco-2 permeable+0.5219
P-glycoprotein substrateNon-substrate0.7609
P-glycoprotein inhibitor IInhibitor0.6464
P-glycoprotein inhibitor IIInhibitor0.5693
Renal organic cation transporterNon-inhibitor0.899
CYP450 2C9 substrateNon-substrate0.7447
CYP450 2D6 substrateNon-substrate0.8061
CYP450 3A4 substrateSubstrate0.5589
CYP450 1A2 substrateNon-inhibitor0.5613
CYP450 2C9 inhibitorInhibitor0.7126
CYP450 2D6 inhibitorNon-inhibitor0.9148
CYP450 2C19 inhibitorInhibitor0.6882
CYP450 3A4 inhibitorInhibitor0.6184
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6711
Ames testNon AMES toxic0.683
CarcinogenicityNon-carcinogens0.7232
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4319 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9911
hERG inhibition (predictor II)Inhibitor0.7079
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-0321900000-b1c610c4a717fdea030e

Targets

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insights and accelerate drug research.
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Details
1. Androgen receptor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
References
  1. FDA Approved Drug Products: Xtandi (enzalutamide) capsules/tablets for oral use 2022 [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [Article]
  2. Poondru S, Ghicavii V, Khosravan R, Manchandani P, Heo N, Moy S, Wojtkowski T, Patton M, Haas GP: Effect of enzalutamide on PK of P-gp and BCRP substrates in cancer patients: CYP450 induction may not always predict overall effect on transporters. Clin Transl Sci. 2022 May;15(5):1131-1142. doi: 10.1111/cts.13229. Epub 2022 Feb 4. [Article]
  3. Flockhart Table of Drug Interactions [Link]
  4. FDA Approved Drug Products: Xtandi (enzalutamide) capsules/tablets for oral use 2022 [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Gibbons JA, de Vries M, Krauwinkel W, Ohtsu Y, Noukens J, van der Walt JS, Mol R, Mordenti J, Ouatas T: Pharmacokinetic Drug Interaction Studies with Enzalutamide. Clin Pharmacokinet. 2015 Oct;54(10):1057-69. doi: 10.1007/s40262-015-0283-1. [Article]
  2. FDA table of interactions [Link]
  3. Enzalutamide FDA label [Link]
  4. Flockhart Table of Drug Interactions [Link]
  5. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Golshayan AR, Antonarakis ES: Enzalutamide: an evidence-based review of its use in the treatment of prostate cancer. Core Evid. 2013;8:27-35. doi: 10.2147/CE.S34747. Epub 2013 Apr 4. [Article]
  2. Flockhart Table of Drug Interactions [Link]
  3. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  4. FDA Approved Drug Products: Xtandi (enzalutamide) capsules/tablets for oral use 2022 [Link]
  5. Enzalutamide FDA label [File]
  6. Xtandi Monograph [File]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Gibbons JA, de Vries M, Krauwinkel W, Ohtsu Y, Noukens J, van der Walt JS, Mol R, Mordenti J, Ouatas T: Pharmacokinetic Drug Interaction Studies with Enzalutamide. Clin Pharmacokinet. 2015 Oct;54(10):1057-69. doi: 10.1007/s40262-015-0283-1. [Article]
  2. Flockhart Table of Drug Interactions [Link]
  3. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  4. FDA Approved Drug Products: Xtandi (enzalutamide) capsules/tablets for oral use 2022 [Link]
  5. Ezalutamide FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Hutson PR: Enzalutamide: A Step Towards Pharmacokinetic-Based Dosing in Men with Metastatic Castration-Resistant Prostate Cancer. Clin Pharmacokinet. 2015 Oct;54(10):989-91. doi: 10.1007/s40262-015-0293-z. [Article]
  2. Poondru S, Ghicavii V, Khosravan R, Manchandani P, Heo N, Moy S, Wojtkowski T, Patton M, Haas GP: Effect of enzalutamide on PK of P-gp and BCRP substrates in cancer patients: CYP450 induction may not always predict overall effect on transporters. Clin Transl Sci. 2022 May;15(5):1131-1142. doi: 10.1111/cts.13229. Epub 2022 Feb 4. [Article]
  3. FDA Approved Drug Products: Xtandi (enzalutamide) capsules/tablets for oral use 2022 [Link]
  4. Enzalutamide FDA Review [File]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inducer
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. FDA table of interactions [Link]
  2. Flockhart Table of Drug Interactions [Link]
  3. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  4. Health Canada Approved Drug Products: Xtandi (enzalutamide) capsules/tablets for oral use 2022 [Link]
  5. Xtandi monograph [File]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. FDA Approved Drug Products: Xtandi (enzalutamide) capsules/tablets for oral use 2022 [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Poondru S, Ghicavii V, Khosravan R, Manchandani P, Heo N, Moy S, Wojtkowski T, Patton M, Haas GP: Effect of enzalutamide on PK of P-gp and BCRP substrates in cancer patients: CYP450 induction may not always predict overall effect on transporters. Clin Transl Sci. 2022 May;15(5):1131-1142. doi: 10.1111/cts.13229. Epub 2022 Feb 4. [Article]
  2. FDA Approved Drug Products: Xtandi (enzalutamide) capsules/tablets for oral use 2022 [Link]

Drug created at June 05, 2013 05:12 / Updated at December 01, 2022 23:18