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Identification
NameNorethindrone
Accession NumberDB00717  (APRD00679)
Typesmall molecule
Groupsapproved
Description

A synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
17α-ethinyl-19-nortestosteroneNot AvailableNot Available
19-nor-17α-ethynyltestosteroneNot AvailableNot Available
19-NorethisteroneNot AvailableNot Available
NorethisteroneNot AvailableINN
NorethisteronumLatinINN
NoretisteronaSpanishINN
Salts
Name/CAS Structure Properties
Norethindrone Acetate
Thumb
  • InChI Key: IMONTRJLAWHYGT-ZCPXKWAGSA-N
  • Monoisotopic Mass: 340.203844762
  • Average Mass: 340.4559
DBSALT000129
Brand names
NameCompany
CamilaNot Available
MicronorNot Available
Primolut-NNot Available
Brand mixtures
Brand NameIngredients
Brevicon 0.5/35 (21 day)Ethinyl Estradiol + Norethindrone
Brevicon 0.5/35 (28 day)Ethinyl Estradiol + Norethindrone
Brevicon 0.5/35 Tablets (21 day)Ethinyl Estradiol + Norethindrone
Brevicon 0.5/35 Tablets (28 day)Ethinyl Estradiol + Norethindrone
Brevicon 1/35 Tablets (21 day)Ethinyl Estradiol + Norethindrone
Brevicon 1/35 Tablets (28 day)Ethinyl Estradiol + Norethindrone
Estalis 140/50 McgEstradiol + Norethindrone Acetate
Estalis 250/50 McgEstradiol + Norethindrone Acetate
Estalis SequiEstradiol + Norethindrone Acetate
EstracombEstradiol + Norethindrone Acetate
Femhrt 1/5Ethinyl Estradiol + Norethindrone Acetate
Lo Minastrin Norethindrone acetate, ethinyl estradiol, ferrous fumarate
Loestrin 1.5/30 21-day PackEthinyl Estradiol + Norethindrone Acetate
Loestrin 1.5/30 28-day PackEthinyl Estradiol + Norethindrone Acetate
Minestrin 1/20 21Ethinyl Estradiol + Norethindrone Acetate
Minestrin 1/20 28Ethinyl Estradiol + Norethindrone Acetate
Norinyl 1/50 - 21-day packMestranol + Norethindrone
Norinyl 1/50 - 28-day packMestranol + Norethindrone
Norinyl 1/50 (21 day)Mestranol + Norethindrone
Norinyl 1/50 (28 day)Mestranol + Norethindrone
Ortho 0.5/35 Tablets (21 day)Ethinyl Estradiol + Norethindrone
Ortho 0.5/35 Tablets (28 day)Ethinyl Estradiol + Norethindrone
Ortho 1/35 Tablets (21 day)Ethinyl Estradiol + Norethindrone
Ortho 1/35 Tablets (28 day)Ethinyl Estradiol + Norethindrone
Ortho 10/11 Tablets (21 day)Ethinyl Estradiol + Norethindrone
Ortho 10/11 Tablets (28 day)Ethinyl Estradiol + Norethindrone
Ortho 7/7/7 Tablets (21 day)Ethinyl Estradiol + Norethindrone
Ortho 7/7/7 Tablets (28 day)Ethinyl Estradiol + Norethindrone
Ortho-Novum 1/50 Tablets (21 day)Mestranol + Norethindrone
Ortho-Novum 1/50 Tablets (28 day)Mestranol + Norethindrone
Select 1/35 (21 day)Ethinyl Estradiol + Norethindrone
Select 1/35 (28 day)Ethinyl Estradiol + Norethindrone
Synphasic (21 day)Ethinyl Estradiol + Norethindrone
Synphasic (28 day)Ethinyl Estradiol + Norethindrone
Categories
CAS number68-22-4
WeightAverage: 298.4192
Monoisotopic: 298.193280076
Chemical FormulaC20H26O2
InChI KeyInChIKey=VIKNJXKGJWUCNN-XGXHKTLJSA-N
InChI
InChI=1S/C20H26O2/c1-3-20(22)11-9-18-17-6-4-13-12-14(21)5-7-15(13)16(17)8-10-19(18,20)2/h1,12,15-18,22H,4-11H2,2H3/t15-,16+,17+,18-,19-,20-/m0/s1
IUPAC Name
(1S,2R,10R,11S,14R,15S)-14-ethynyl-14-hydroxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
SMILES
[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H]
Mass Specshow(11.3 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassKetosteroids
Direct parentKetosteroids
Alternative parentsHydroxysteroids; Estrogens and Derivatives; Ynones; Tertiary Alcohols; Cyclic Alcohols and Derivatives; Polyamines
Substituentsynone; tertiary alcohol; cyclic alcohol; ketone; polyamine; alcohol; carbonyl group
Classification descriptionThis compound belongs to the ketosteroids. These are steroid derivatives comprising a ketone group attached to steroid skeleton.
Pharmacology
IndicationNorethindrone acetate is indicated for the treatment of secondary amenorrhea, endometriosis, and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer.
PharmacodynamicsNorethindrone is a synthetic oral progestin. It is used for contraception or to treat such conditions as secondary amenorrhea, abnormal uterine bleeding, and endometriosis. As an oral contraceptive, norethindrone is available as either a single agent or in combination with an estrogen. Norethindrone acetate induces secretory changes in an estrogen-primed endometrium. On a weight basis, it is twice as potent as norethindrone.
Mechanism of actionProgestins diffuse freely into target cells and bind to the progesterone receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH surge.
AbsorptionNorethindrone acetate is completely and rapidly deacetylated to norethindrone (NET) after oral administration, and the disposition of norethindrone acetate is indistinguishable from that of orally administered norethindrone. Norethindrone is rapidly absorbed from norethindrone acetate, in which maximum plasma concentration occur 2 hours post-dose (Tmax). When a single dose is given to healthy women, the Cmax is 26.19 ± 6.19 hours. The AUC (0-inf) is 166.90 ± 56.28 ng/mL*h. Absolute oral bioavailability is approximately 64%. The effect of food on the pharmacokinetics of norethindrone acetate is unknown.
Volume of distribution
  • 4 L/kg
Protein bindingNorethindrone is 36% bound to sex hormone-binding globulin and 61% bound to albumin.
Metabolism

Hepatic. Norethindrone is extensively metabolized, primarily via reduction. It also undergoes sulfate and glucuronide conjugation. The majority of metabolites in the circulation are sulfates, with glucuronides accounting for most of the urinary metabolites.

Route of eliminationNorethindrone is excreted in both urine and feces, primarily as metabolites.
Half life8.51 ± 2.19 (when a single dose is given to healthy women)
Clearance
  • 0.4 L/hr/kg [plasma clearance]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9413
Caco-2 permeable + 0.8572
P-glycoprotein substrate Substrate 0.6346
P-glycoprotein inhibitor I Inhibitor 0.5079
P-glycoprotein inhibitor II Non-inhibitor 0.9087
Renal organic cation transporter Non-inhibitor 0.7603
CYP450 2C9 substrate Non-substrate 0.7759
CYP450 2D6 substrate Non-substrate 0.9237
CYP450 3A4 substrate Substrate 0.7415
CYP450 1A2 substrate Non-inhibitor 0.844
CYP450 2C9 substrate Non-inhibitor 0.8688
CYP450 2D6 substrate Non-inhibitor 0.9386
CYP450 2C19 substrate Inhibitor 0.8994
CYP450 3A4 substrate Non-inhibitor 0.8333
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7876
Ames test Non AMES toxic 0.9319
Carcinogenicity Non-carcinogens 0.9417
Biodegradation Not ready biodegradable 0.9512
Rat acute toxicity 1.8788 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8777
hERG inhibition (predictor II) Non-inhibitor 0.7744
Pharmacoeconomics
Manufacturers
  • Parke davis div warner lambert co
  • Barr laboratories inc
  • Glenmark generics ltd
  • Ortho mcneil janssen pharmaceuticals inc
  • Watson laboratories inc
  • Duramed research inc
  • Glenmark generics ltd india
  • Warner Chilcott
Packagers
Dosage forms
FormRouteStrength
TabletOral0.35 mg, 5 mg
Prices
Unit descriptionCostUnit
Ovcon-35 (28) 28 0.4-35 mg-mcg tablet Disp Pack89.09USDdisp
Ovcon-50 28 50-1 mcg-mg tablet Disp Pack89.09USDdisp
Loestrin 1.5/30 (21) 21 1.5-30 mg-mcg tablet Disp Pack79.32USDdisp
Loestrin 1/20 (21) 21 1-20 mg-mcg tablet Disp Pack79.32USDdisp
Loestrin Fe 1/20 28 1-20 mg-mcg tablet Disp Pack79.32USDdisp
Loestrin Fe 1.5/30 28 1.5-30 mg-mcg tablet Disp Pack77.1USDdisp
Loestrin 24 Fe 28 1-20 mg-mcg tablet Disp Pack75.15USDdisp
Nor-QD 28 0.35 mg tablet Disp Pack65.87USDdisp
Tri-Norinyl (28) 28 0.5/1/0.5-35 mg-mcg tablet Disp Pack62.63USDdisp
Ortho-Novum 10/11 (28) 28 35 mcg tablet Disp Pack60.25USDdisp
Modicon (28) 28 0.5-35 mg-mcg tablet Disp Pack59.99USDdisp
Norinyl 1+35 (28) 28 1-35 mg-mcg tablet Disp Pack55.99USDdisp
Ortho-Novum 1/35 (28) 28 1-35 mg-mcg tablet Disp Pack55.99USDdisp
Brevicon (28) 28 0.5-35 mg-mcg tablet Disp Pack53.0USDdisp
Norinyl 1+50 (28) 28 1-50 mg-mcg tablet 1 Disp Pack = 28 Pills52.99USDdisp
Necon 10/11 (28) 28 35 mcg tablet Disp Pack35.99USDdisp
Ortho-Novum 7/7/7 (28) 28 0.5/0.75/1-35 mg-mcg tablet Disp Pack33.99USDdisp
Necon 0.5/35 (28) 28 0.5-35 mg-mcg tablet Disp Pack32.99USDdisp
Necon 1/35 (28) 28 1-35 mg-mcg tablet Disp Pack31.99USDdisp
Loestrin fe 1-20 tablet5.23USDtablet
Loestrin 21 1.5-30 tablet3.66USDtablet
Loestrin 21 1-20 tablet3.66USDtablet
Aygestin 5 mg tablet3.27USDtablet
Ovcon-35 28 tablet3.06USDtablet
Loestrin fe 1.5-30 tablet2.75USDtablet
Norethindrone Acetate 5 mg tablet2.75USDtablet
Norethindrone 5 mg tablet2.65USDtablet
Ovcon-50 28 tablet2.62USDtablet
Micronor tablet2.44USDtablet
Nor-q-d tablet2.24USDtablet
Necon 1-35-28 tablet2.11USDtablet
Modicon 28 tablet2.07USDtablet
Tri-norinyl 28 tablet2.01USDtablet
Ortho-novum 1-35-28 tablet1.9USDtablet
Brevicon 28 tablet1.8USDtablet
Norinyl 1+35-28 tablet1.73USDtablet
Norinyl 1+50-28 tablet1.73USDtablet
Demulen 1-50-21 tablet1.67USDtablet
Ortho-novum 7-7-7-21 tablet1.4USDtablet
Errin 0.35 mg tablet1.34USDtablet
Ortho-novum 7/7/7-28 tablet1.33USDtablet
Camila tablet1.32USDtablet
Jolivette tablet1.32USDtablet
Nora-be tablet1.32USDtablet
Norethindrone 0.35 mg tablet1.32USDtablet
Demulen 1-50-28 tablet1.29USDtablet
Ortho micronor tablet1.23USDtablet
Necon 0.5-35-28 tablet1.15USDtablet
Necon 7-7-7-28 tablet1.15USDtablet
Necon 1-50-28 tablet1.05USDtablet
Ortho-novum 7-7-7-28 tablet1.02USDtablet
Micronor (28 Day) 0.35 mg Tablet0.66USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point203.5 °CPhysProp
water solubility7.04 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.97HANSCH,C ET AL. (1995)
logS-4.57ADME Research, USCD
Predicted Properties
PropertyValueSource
water solubility6.68e-03 g/lALOGPS
logP2.72ALOGPS
logP3.22ChemAxon
logS-4.7ALOGPS
pKa (strongest acidic)17.59ChemAxon
pKa (strongest basic)-1.7ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count1ChemAxon
polar surface area37.3ChemAxon
rotatable bond count0ChemAxon
refractivity87.42ChemAxon
polarizability34.71ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. FDA label
External Links
ResourceLink
KEGG DrugD00182
KEGG CompoundC05028
PubChem Compound6230
PubChem Substance46504816
ChemSpider5994
ChEBI7627
ChEMBLCHEMBL1162
Therapeutic Targets DatabaseDAP001212
PharmGKBPA450651
HETNDR
Drug Product Database23760
RxListhttp://www.rxlist.com/cgi/generic2/norethin.htm
Drugs.comhttp://www.drugs.com/cdi/norethindrone.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/ayg1666.shtml
WikipediaNorethindrone
ATC CodesG03AC01
AHFS Codes
  • 68:12.00
PDB EntriesNot Available
FDA labelshow(322 KB)
MSDSshow(73.9 KB)
Interactions
Drug Interactions
Drug
AcitretinAcitretine may cause a loss of contraceptive effect
AmobarbitalThis product may cause a slight decrease of contraceptive effect
AprobarbitalThis product may cause a slight decrease of contraceptive effect
ArtemetherArtemether may decrease the effectiveness of norethindrone by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
BexaroteneBexarotene may decrease the serum concentration of Contraceptives (Progestins). Since bexarotene is teratogenic and can lower serum concentrations of norethindrone, it is advised that women of childbearing potential use two forms of contraception (including at least one non-hormonal form).
BosentanBosentan may decrease the contraceptive effect of norethindrone. Hormonal contraception should not be relied on alone during concomitant therapy with bosentan.
ButabarbitalThis product may cause a slight decrease of contraceptive effect
ButalbitalThis product may cause a slight decrease of contraceptive effect
ButethalThis product may cause a slight decrease of contraceptive effect
CarbamazepineThis product may cause a slight decrease of contraceptive effect
ColesevelamBile Acid Sequestrants may decrease the serum concentration of Contraceptives (Progestins). Administer oral progestin-containing contraceptives at least 1-4 hours prior to or 4-6 hours after administration of a bile acid sequestrant. Consider alternatives in order to avoid this combination when possible, due to the risk for impaired contraceptive effectiveness.
EthotoinThis product may cause a slight decrease of contraceptive effect
FosphenytoinThis product may cause a slight decrease of contraceptive effect
GriseofulvinThis product may cause a slight decrease of contraceptive effect
HeptabarbitalThis product may cause a slight decrease of contraceptive effect
HexobarbitalThis product may cause a slight decrease of contraceptive effect
LamotrigineThe oral contraceptive decreases the effect of lamotrigine
MephenytoinThis product may cause a slight decrease of contraceptive effect
MethohexitalThis product may cause a slight decrease of contraceptive effect
MethylphenobarbitalThis product may cause a slight decrease of contraceptive effect
PentobarbitalThis product may cause a slight decrease of contraceptive effect
PhenobarbitalThis product may cause a slight decrease of contraceptive effect
PhenytoinThis product may cause a slight decrease of contraceptive effect
PioglitazonePossible loss of contraceptive effect
PrimidoneThis product may cause a slight decrease of contraceptive effect
RifabutinRifabutin may decrease the contraceptive effect of norethindrone. Hormonal contraception should not be solely relied on alone during concomitant therapy with rifabutin.
RifampicinThis product may cause a slight decrease of contraceptive effect
RifapentineThis product may cause a slight decrease of contraceptive effect
RufinamideRufinamide decreases plasma concentrations of norethindrone, thus consider therapy modification
SecobarbitalThis product may cause a slight decrease of contraceptive effect
St. John's WortSt. John's Wort could reduce the contraceptive effect
TalbutalThis product may cause a slight decrease of contraceptive effect
ThiopentalThiopental may decrease the effect of Norethindrone. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.
TizanidineThe contraceptive increases the effect of tizanidine
TretinoinOral Tretinoin may decrease the effect of oral contraceptive, Norethindrone. An alternate form of contraception should be used during concomitant therapy.
TroglitazonePossible loss of contraceptive effect
WarfarinNorethindrone may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if norethindrone is initiated, discontinued or dose changed.
Food Interactions
  • Take without regard to meals.

1. Progesterone receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Progesterone receptor P06401 Details

References:

  1. Mendoza-Rodriguez CA, Camacho-Arroyo I, Garcia GA, Cerbon MA: Variations of progesterone receptor and c-fos gene expression in the rat uterus after treatment with norethisterone and its A-ring reduced metabolites. Contraception. 1999 May;59(5):339-43. Pubmed
  2. Madauss KP, Deng SJ, Austin RJ, Lambert MH, McLay I, Pritchard J, Short SA, Stewart EL, Uings IJ, Williams SP: Progesterone receptor ligand binding pocket flexibility: crystal structures of the norethindrone and mometasone furoate complexes. J Med Chem. 2004 Jun 17;47(13):3381-7. Pubmed
  3. Garcia-Becerra R, Cooney AJ, Borja-Cacho E, Lemus AE, Perez-Palacios G, Larrea F: Comparative evaluation of androgen and progesterone receptor transcription selectivity indices of 19-nortestosterone-derived progestins. J Steroid Biochem Mol Biol. 2004 Jun;91(1-2):21-7. Pubmed
  4. Mirkin S, Wong BC, Archer DF: Effect of 17 beta-estradiol, progesterone, synthetic progestins, tibolone, and tibolone metabolites on vascular endothelial growth factor mRNA in breast cancer cells. Fertil Steril. 2005 Aug;84(2):485-91. Pubmed
  5. Pasapera AM, Cerbon MA, Castro I, Gutierrez R, Camacho-Arroyo I, Garcia GA, Perez-Palacios G: Norethisterone metabolites modulate the uteroglobin and progesterone receptor gene expression in prepubertal rabbits. Biol Reprod. 1995 Feb;52(2):426-32. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

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. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

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. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

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. Epub 2009 Nov 24. Pubmed

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. FDA label

2. Sex hormone-binding globulin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Sex hormone-binding globulin P04278 Details

References:

  1. FDA label

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Kim WY, Benet LZ: P-glycoprotein (P-gp/MDR1)-mediated efflux of sex-steroid hormones and modulation of P-gp expression in vitro. Pharm Res. 2004 Jul;21(7):1284-93. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11