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Identification
NameDutasteride
Accession NumberDB01126  (APRD00385)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Dutasteride belongs to a class of drugs called 5-alpha-reductase inhibitors, which block the action of the 5-alpha-reductase enzymes that convert testosterone into dihydrotestosterone (DHT). Finasteride also belongs to this group, but while dutasteride inhibits both isoforms of 5-alpha reductase, finasteride inhibits only one. Even so, a clinical study done by GlaxoSmithKline, the EPICS trial, did not find dutasteride to be more effective than finasteride in treating BPH. [Wikipedia]

Structure
Thumb
Synonyms
(5alpha,17beta)-N-(2,5-Bis(trifluoromethyl)phenyl)-3-oxo-4-azaandrost-1-ene-17-carboxamide
alpha,alpha,alpha,Alpha',alpha',alpha'-hexafluoro-3-oxo-4-aza-5alpha-androst-1-ene-17beta-carboxy-2',5'-xylidide
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act Dutasteridecapsule0.5 mgoralActavis Pharma Company2014-09-05Not applicableCanada
Avodartcapsule, liquid filled.5 mg/1oralGlaxo Smith Kline Llc2002-12-10Not applicableUs
Avodartcapsule0.5 mgoralGlaxosmithkline Inc2003-11-14Not applicableCanada
Avodartcapsule, liquid filled.5 mg/1oralA S Medication Solutions2002-12-10Not applicableUs
Avodartcapsule, liquid filled.5 mg/1oralAvera Mc Kennan Hospital2015-03-23Not applicableUs
Avodartcapsule, liquid filled.5 mg/1oralPhysicians Total Care, Inc.2004-07-16Not applicableUs
Avodartcapsule, liquid filled.5 mg/1oralLake Erie Medical & Surgcial Supply DBA Quality Care Products LLC2012-03-26Not applicableUs
Dutasteridecapsule0.5 mgoralSanis Health Inc2015-07-21Not applicableCanada
Dutasteridecapsule0.5 mgoralSivem Pharmaceuticals Ulc2014-10-08Not applicableCanada
Dutasteridecapsule0.5 mgoralPro Doc Limitee2014-07-22Not applicableCanada
Dutasteride Capsulescapsule0.5 mgoralStrides Arcolab LimitedNot applicableNot applicableCanada
Med-dutasteridecapsule0.5 mgoralGeneric Medical Partners Inc2014-10-10Not applicableCanada
Mint-dutasteridecapsule0.5 mgoralMint Pharmaceuticals Inc2014-09-19Not applicableCanada
PMS-dutasteridecapsule0.5 mgoralPharmascience Inc2014-07-21Not applicableCanada
Riva-dutasteridecapsule0.5 mgoralLaboratoire Riva Inc2014-09-18Not applicableCanada
Sandoz Dutasteridecapsule0.5 mgoralSandoz Canada IncorporatedNot applicableNot applicableCanada
Sandoz Dutasteride Capsulecapsule0.5 mgoralSandoz Canada Incorporated2014-07-22Not applicableCanada
Teva-dutasteridecapsule0.5 mgoralTeva Canada Limited2014-07-16Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-dutasteridecapsule0.5 mgoralApotex Inc2014-07-18Not applicableCanada
Dutasteridecapsule.5 mg/1oralRoxane Laboratories, Inc.2015-11-23Not applicableUs
Dutasteridecapsule, liquid filled.5 mg/1oralApotex Corp.2015-11-25Not applicableUs
Dutasteridecapsule, liquid filled.5 mg/1oralIntergel Pharmaceuticals Inc2002-12-10Not applicableUs
Dutasteridecapsule.5 mg/1oralBreckenridge Pharmaceutical, Inc.2015-11-20Not applicableUs
Dutasteridecapsule.5 mg/1oralProficient Rx LP2015-11-20Not applicableUs
Dutasteridecapsule.5 mg/1oralAv Kare, Inc.2015-11-30Not applicableUs
Dutasteridecapsule.5 mg/1oralActavis Pharma, Inc.2015-11-20Not applicableUs
Dutasteridecapsule.5 mg/1oralAmneal Pharmaceuticals of New York, LLC2015-11-02Not applicableUs
Dutasteridecapsule, liquid filled.5 mg/1oralImpax Generics2015-11-20Not applicableUs
Dutasteridecapsule, liquid filled.5 mg/1oralRising Pharmaceuticals, Inc.2015-11-20Not applicableUs
Dutasteridecapsule, liquid filled.5 mg/1oralTeva Pharmaceuticals USA Inc2015-10-09Not applicableUs
Dutasteridecapsule, liquid filled.5 mg/1oralStrides Arcolab Limited2015-11-20Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
Dutasteride and Tamsulosin HydrochloridePar Pharmaceutical
JalynGlaxo Smith Kline Llc
SaltsNot Available
Categories
UNIIO0J6XJN02I
CAS number164656-23-9
WeightAverage: 528.5297
Monoisotopic: 528.221147444
Chemical FormulaC27H30F6N2O2
InChI KeyInChIKey=JWJOTENAMICLJG-QWBYCMEYSA-N
InChI
InChI=1S/C27H30F6N2O2/c1-24-11-9-17-15(4-8-21-25(17,2)12-10-22(36)35-21)16(24)6-7-19(24)23(37)34-20-13-14(26(28,29)30)3-5-18(20)27(31,32)33/h3,5,10,12-13,15-17,19,21H,4,6-9,11H2,1-2H3,(H,34,37)(H,35,36)/t15-,16-,17-,19+,21+,24-,25+/m0/s1
IUPAC Name
(1S,2R,7R,10S,11S,14S,15S)-N-[2,5-bis(trifluoromethyl)phenyl]-2,15-dimethyl-5-oxo-6-azatetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-3-ene-14-carboxamide
SMILES
[H][C@@]1(CC[C@@]2([H])[C@]3([H])CC[C@@]4([H])NC(=O)C=C[C@]4(C)[C@@]3([H])CC[C@]12C)C(=O)NC1=CC(=CC=C1C(F)(F)F)C(F)(F)F
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as oxosteroids. These are steroid derivatives carrying a C=O group attached to steroid skeleton.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassOxosteroids
Direct ParentOxosteroids
Alternative Parents
Substituents
  • 3-oxo-4-azasteroid
  • 3-oxo-5-alpha-steroid
  • Oxosteroid
  • 3-oxosteroid
  • Azasteroid
  • 4-azasteroid
  • N-arylamide
  • Tetrahydropyridine
  • Benzenoid
  • Monocyclic benzene moiety
  • Secondary carboxylic acid amide
  • Lactam
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate gland to improve symptoms, and reduce the risk of acute urinary retention and the need for surgery.
PharmacodynamicsDutasteride is a synthetic 4-azasteroid compound that is a selective inhibitor of both the type 1 and type 2 isoforms of steroid 5 alpha-reductase (5AR), intracellular enzymes that convert testosterone to 5 alpha-dihydrotestosterone (DHT). Type I 5a-reductase is predominant in the sebaceous glands of most regions of skin, including scalp, and liver. Type I 5a-reductase is responsible for approximately one-third of circulating DHT. The Type II 5a-reductase isozyme is primarily found in prostate, seminal vesicles, epididymides, and hair follicles as well as liver, and is responsible for two-thirds of circulating DHT.
Mechanism of actionDutasteride inhibits the conversion of testosterone to 5 alpha-dihydrotestosterone (DHT), which is the androgen primarily responsible for the initial development and subsequent enlargement of the prostate gland. Testosterone is converted to DHT by the enzyme 5 alpha-reductase, which exists as 2 isoforms, type 1 and type 2. Dutasteride is a competitive and specific inhibitor of both type 1 and type 2 5 alpha-reductase isoenzymes, with which it forms a stable enzyme complex. Dissociation from this complex has been evaluated under in vitro and in vivo conditions and is extremely slow. Dutasteride does not bind to the human androgen receptor.
Related Articles
Absorption60%
Volume of distribution
  • 300 to 500 L
Protein bindingHighly bound to albumin (99%) and α-1 acid glycoprotein (96.6%).
Metabolism

Hepatic. Extensively metabolized by CYP3A4 and CYP3A5 to active metabolites.

Route of eliminationDutasteride is extensively metabolized in humans. Dutasteride and its metabolites were excreted mainly in feces.
Half life5 weeks
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9884
Caco-2 permeable-0.5223
P-glycoprotein substrateSubstrate0.747
P-glycoprotein inhibitor IInhibitor0.7278
P-glycoprotein inhibitor IINon-inhibitor0.6085
Renal organic cation transporterNon-inhibitor0.8299
CYP450 2C9 substrateNon-substrate0.8077
CYP450 2D6 substrateNon-substrate0.9117
CYP450 3A4 substrateSubstrate0.7186
CYP450 1A2 substrateNon-inhibitor0.8089
CYP450 2C9 inhibitorInhibitor0.5412
CYP450 2D6 inhibitorNon-inhibitor0.8391
CYP450 2C19 inhibitorInhibitor0.6287
CYP450 3A4 inhibitorNon-inhibitor0.6506
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5913
Ames testNon AMES toxic0.6677
CarcinogenicityNon-carcinogens0.9149
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6885 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9829
hERG inhibition (predictor II)Non-inhibitor0.574
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Capsuleoral0.5 mg
Capsuleoral.5 mg/1
Capsule, liquid filledoral.5 mg/1
Capsuleoral
Capsule (immediate and extended release)oral
Prices
Unit descriptionCostUnit
Avodart 0.5 mg capsule4.12USD capsule
Avodart 0.5 mg softgel4.06USD softgel capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2170047 No2004-11-092014-09-16Canada
CA2171329 No2004-11-232014-09-16Canada
US5565467 No1995-11-202015-11-20Us
US5846976 No1993-09-172013-09-17Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP6.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000908 mg/mLALOGPS
logP5.45ALOGPS
logP5.79ChemAxon
logS-5.8ALOGPS
pKa (Strongest Acidic)12.56ChemAxon
pKa (Strongest Basic)2.17ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.2 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity127.9 m3·mol-1ChemAxon
Polarizability50.13 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Manne Reddy, “Forms of dutasteride and methods for preparation thereof.” U.S. Patent US20040077673, issued April 22, 2004.

US20040077673
General References
  1. Keam SJ, Scott LJ: Dutasteride: a review of its use in the management of prostate disorders. Drugs. 2008;68(4):463-85. [PubMed:18318566 ]
  2. Shah SK, Trump DL, Sartor O, Tan W, Wilding GE, Mohler JL: Phase II study of Dutasteride for recurrent prostate cancer during androgen deprivation therapy. J Urol. 2009 Feb;181(2):621-6. doi: 10.1016/j.juro.2008.10.014. Epub 2008 Dec 16. [PubMed:19091347 ]
External Links
ATC CodesG04CA52G04CB02
AHFS Codes
  • 92:00.00
PDB EntriesNot Available
FDA labelDownload (462 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AtazanavirThe serum concentration of Dutasteride can be increased when it is combined with Atazanavir.
BoceprevirThe serum concentration of Dutasteride can be increased when it is combined with Boceprevir.
CeritinibThe serum concentration of Dutasteride can be increased when it is combined with Ceritinib.
ClarithromycinThe serum concentration of Dutasteride can be increased when it is combined with Clarithromycin.
CobicistatThe serum concentration of Dutasteride can be increased when it is combined with Cobicistat.
DarunavirThe serum concentration of Dutasteride can be increased when it is combined with Darunavir.
IdelalisibThe serum concentration of Dutasteride can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Dutasteride can be increased when it is combined with Indinavir.
ItraconazoleThe serum concentration of Dutasteride can be increased when it is combined with Itraconazole.
KetoconazoleThe serum concentration of Dutasteride can be increased when it is combined with Ketoconazole.
NefazodoneThe serum concentration of Dutasteride can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Dutasteride can be increased when it is combined with Nelfinavir.
PosaconazoleThe serum concentration of Dutasteride can be increased when it is combined with Posaconazole.
RitonavirThe serum concentration of Dutasteride can be increased when it is combined with Ritonavir.
SaquinavirThe serum concentration of Dutasteride can be increased when it is combined with Saquinavir.
TelaprevirThe serum concentration of Dutasteride can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Dutasteride can be increased when it is combined with Telithromycin.
VoriconazoleThe serum concentration of Dutasteride can be increased when it is combined with Voriconazole.
Food Interactions
  • Take without regard to meals.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Electron carrier activity
Specific Function:
Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.
Gene Name:
SRD5A1
Uniprot ID:
P18405
Molecular Weight:
29458.18 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Xu Y, Dalrymple SL, Becker RE, Denmeade SR, Isaacs JT: Pharmacologic basis for the enhanced efficacy of dutasteride against prostatic cancers. Clin Cancer Res. 2006 Jul 1;12(13):4072-9. [PubMed:16818707 ]
  3. Rathnayake D, Sinclair R: Male androgenetic alopecia. Expert Opin Pharmacother. 2010 Jun;11(8):1295-304. doi: 10.1517/14656561003752730. [PubMed:20426708 ]
  4. Aggarwal S, Thareja S, Verma A, Bhardwaj TR, Kumar M: An overview on 5alpha-reductase inhibitors. Steroids. 2010 Feb;75(2):109-53. doi: 10.1016/j.steroids.2009.10.005. Epub 2009 Oct 30. [PubMed:19879888 ]
  5. Smith AB, Carson CC: Finasteride in the treatment of patients with benign prostatic hyperplasia: a review. Ther Clin Risk Manag. 2009 Jun;5(3):535-45. Epub 2009 Jul 12. [PubMed:19707263 ]
  6. Goldenberg L, So A, Fleshner N, Rendon R, Drachenberg D, Elhilali M: The role of 5-alpha reductase inhibitors in prostate pathophysiology: Is there an additional advantage to inhibition of type 1 isoenzyme? Can Urol Assoc J. 2009 Jun;3(3 Suppl 2):S109-14. [PubMed:19543428 ]
  7. Keam SJ, Scott LJ: Dutasteride: a review of its use in the management of prostate disorders. Drugs. 2008;68(4):463-85. [PubMed:18318566 ]
  8. Rittmaster RS, Fleshner NE, Thompson IM: Pharmacological approaches to reducing the risk of prostate cancer. Eur Urol. 2009 May;55(5):1064-73. doi: 10.1016/j.eururo.2009.01.037. Epub 2009 Feb 5. [PubMed:19200641 ]
  9. Shah SK, Trump DL, Sartor O, Tan W, Wilding GE, Mohler JL: Phase II study of Dutasteride for recurrent prostate cancer during androgen deprivation therapy. J Urol. 2009 Feb;181(2):621-6. doi: 10.1016/j.juro.2008.10.014. Epub 2008 Dec 16. [PubMed:19091347 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Sterol 5-alpha reductase activity
Specific Function:
Converts testosterone (T) into 5-alpha-dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.
Gene Name:
SRD5A2
Uniprot ID:
P31213
Molecular Weight:
28393.015 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Rathnayake D, Sinclair R: Male androgenetic alopecia. Expert Opin Pharmacother. 2010 Jun;11(8):1295-304. doi: 10.1517/14656561003752730. [PubMed:20426708 ]
  3. Aggarwal S, Thareja S, Verma A, Bhardwaj TR, Kumar M: An overview on 5alpha-reductase inhibitors. Steroids. 2010 Feb;75(2):109-53. doi: 10.1016/j.steroids.2009.10.005. Epub 2009 Oct 30. [PubMed:19879888 ]
  4. Smith AB, Carson CC: Finasteride in the treatment of patients with benign prostatic hyperplasia: a review. Ther Clin Risk Manag. 2009 Jun;5(3):535-45. Epub 2009 Jul 12. [PubMed:19707263 ]
  5. Goldenberg L, So A, Fleshner N, Rendon R, Drachenberg D, Elhilali M: The role of 5-alpha reductase inhibitors in prostate pathophysiology: Is there an additional advantage to inhibition of type 1 isoenzyme? Can Urol Assoc J. 2009 Jun;3(3 Suppl 2):S109-14. [PubMed:19543428 ]
  6. Keam SJ, Scott LJ: Dutasteride: a review of its use in the management of prostate disorders. Drugs. 2008;68(4):463-85. [PubMed:18318566 ]
  7. Xu Y, Dalrymple SL, Becker RE, Denmeade SR, Isaacs JT: Pharmacologic basis for the enhanced efficacy of dutasteride against prostatic cancers. Clin Cancer Res. 2006 Jul 1;12(13):4072-9. [PubMed:16818707 ]
  8. Rittmaster RS, Fleshner NE, Thompson IM: Pharmacological approaches to reducing the risk of prostate cancer. Eur Urol. 2009 May;55(5):1064-73. doi: 10.1016/j.eururo.2009.01.037. Epub 2009 Feb 5. [PubMed:19200641 ]
  9. Shah SK, Trump DL, Sartor O, Tan W, Wilding GE, Mohler JL: Phase II study of Dutasteride for recurrent prostate cancer during androgen deprivation therapy. J Urol. 2009 Feb;181(2):621-6. doi: 10.1016/j.juro.2008.10.014. Epub 2008 Dec 16. [PubMed:19091347 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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 unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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Drug created on June 13, 2005 07:24 / Updated on July 23, 2016 01:53