Ethinylestradiol

Identification

Summary

Ethinylestradiol is an estradiol used as a contraceptive.

Brand Names

Afirmelle 28 Day, Alesse, Altavera 28 Day, Alyacen 1/35, Alyacen 7/7/7, Amethia 91 Day, Amethyst, Annovera, Apri 28 Day, Aranelle 28, Ashlyna 91 Day, Aubra 28 Day, Aurovela, Aurovela Fe, Aviane 28, Ayuna 28 Day Pack, Azurette 28 Day, Balcoltra 28 Day, Balziva 28 Day, Bekyree 28 Day, Beyaz 28 Day, Blisovi 21 Fe 1.5/30 28 Day Pack, Blisovi 21 Fe 1/20 28 Day Pack, Blisovi 24 Fe 1/20 28 Day, Brevicon, Briellyn 28 Day, Camrese 91 Day, Camreselo 91 Day, Caziant 28 Day, Cesia 28 Day, Charlotte 24 Fe Chewable 28 Day, Chateal 28 Day, Cléo -35, Cryselle 28, Cyclafem 1/35 28 Day, Cyclafem 7/7/7 28 Day, Cyestra-35, Cyonanz 28 Day, Cyred 28 Day, Dasetta 1/35 28 Day, Dasetta 7/7/7 28 Day, Daysee 91 Day, Delyla 28 Day, Diane, Dolishale 28 Day, Elinest 28 Day, Eluryng, Emoquette, Enilloring, Enpresse 28 Day, Enskyce 28 Day, Estarylla 28 Day, Evra, Falmina 28 Day, Fayosim 91 Day, Femcon Fe 28 Day, Femhrt 0.5/2.5 28 Day, Femynor 28 Day, Finzala 24 Fe Chewable 28 Day, Freya, Fyavolv, Gemmily 28 Day, Gianvi 28-day, Hailey 1.5/30 21 Day, Hailey 24 Fe 28 Day, Hailey Fe 1.5/30 28 Day, Hailey Fe 1/20 28 Day, Iclevia 91 Day, Indayo, Introvale 91 Day, Isibloom 28 Day, Jaimiess 91 Day, Jasmiel 28 Day, Jinteli, Jolessa 91 Day, Joyeaux 28 Day, Juleber 28 Day, Junel 1.5/30 21 Day, Junel 1/20 21 Day, Junel Fe 1.5/30 28 Day, Junel Fe 1/20 28 Day, Junel Fe 24 1/20 28 Day, Kaitlib Fe 28 Day, Kalliga, Kariva 28 Day, Kelnor 1/35 28 Day, Kelnor 1/50 28 Day, Kurvelo, Larin 1.5/30, Larin 1/20, Larin 24 Fe 1/20, Larin Fe 1.5/30, Larin Fe 1/20, Layolis Fe 28, Leena 28 Day, Levonest 28 Day, Levora 0.15/30 28 Day, Linessa, Lo Loestrin Fe 28 Day, Lo Simpesse, Lo-zumandimine 28 Day, Lo/ovral 28 Day, LoJaimiess, Loestrin 1.5/30 21 Day, Loestrin 24 Fe 28 Day, Loestrin Fe 1/20 28 Day, Lolo, Lomedia 24 Fe, Loryna, Loseasonique, Low-ogestrel 28 Day, Lutera 28 Day, Marlissa 28 Day, Marvelon, Melodetta 24 Fe Chewable 28 Day, Merzee 28 Day, Mibelas 24 Fe Chewable 28 Day, Microgestin 1.5/30 21 Day, Microgestin 1/20 21 Day, Microgestin 24 Fe 28 Day, Microgestin Fe 1.5/30 28 Day, Microgestin Fe 1/20 28 Day, Mili 28 Day, Min-ovral, Minastrin 24 Fe Chewable 28 Day, Mircette 28 Day, Mono-linyah 28 Day, Mononessa 28 Day, Myzilra 28 Day, Necon 0.5/35 28 Day, Necon 1/35 28 Day, Necon 7/7/7 28 Day, Nexesta Fe 28 Day, Nikki 28 Day, Nortrel 1/35 21 Day, Nortrel 1/35 28 Day, Nortrel 7/7/7 28 Day, Nuvaring, Nylia 1/35 28 Day, Nylia 7/7/7 28 Day, Nymyo 28 Day, Ocella 28 Day, Orsythia 28 Day, Ortho Tri-cyclen 28 Day, Ortho Tri-cyclen Lo 28 Day, Ortho-novum 7/7/7 28 Day, Philith 28 Day, Pimtrea Pack, Pirmella 1/35 28 Day, Pirmella 7/7/7 28 Day, Portia 28 Day, Previfem 28 Day, Quartette 91 Day Pack, Reclipsen, Rhuzdah 28 Day, Rivelsa 91 Day, Safyral 28 Day, Seasonale, Seasonique, Select, Setlakin 91 Day, Simliya, Simpesse, Sprintec 28 Day, Sronyx 28 Day, Syeda 28 Day, Synphasic, Tarina 24 Fe 1/20 28 Day, Tarina Fe 1/20 28 Day, Taysofy 28 Day, Taytulla 28 Day, Tilia Fe, Tri Femynor 28 Day, Tri-LO- Estarylla 28 Day, Tri-LO-marzia 28-day, Tri-LO-mili, Tri-Lo-Sprintec, Tri-estarylla 28 Day, Tri-legest 28 Day, Tri-linyah, Tri-mili 28 Day, Tri-nymyo 28 Day Pack, Tri-previfem 28 Day, Tri-sprintec 28 Day, Tri-vylibra 28 Day, Tri-vylibra Lo 28 Day, Trinessa 28 Day, Trinessa Lo 28 Day, Triquilar, Trivora 28 Day, Turqoz 28 Day, Twirla 3 Count Weekly Patch, Tyblume 28 Day, Tydemy 28 Day, Velivet 28 Day, Vestura, Vienva 28 Day, Viorele 28 Day, Volnea 28 Day, Vyfemla 28 Day, Vylibra 28 Day, Wera 28 Day, Wymzya Fe 28 Day, Xulane, Yasmin, Yasmin 28 Day, Yaz 28 Day, Yaz Plus, Zafemy, Zarah, Zenchent, Zovia 1/35e 28 Day, Zovia 1/50e 28 Day, Zumandimine 28 Day

Generic Name

Ethinylestradiol

DrugBank Accession Number

DB00977

Background

Ethinylestradiol was first synthesized in 1938 by Hans Herloff Inhoffen and Walter Hohlweg at Schering.¹ It was developed in an effort to create an estrogen with greater oral bioavailability.¹ These properties were achieved by the substitution of an ethinyl group at carbon 17 of estradiol.¹ Ethinylestradiol soon replaced mestranol in contraceptive pills.¹

Ethinylestradiol was granted FDA approval on 25 June 1943.¹⁴

Type

Small Molecule

Groups

Approved

Structure

Similar Structures

Weight: Average: 296.4034
Monoisotopic: 296.177630012
Chemical Formula: C₂₀H₂₄O₂

Synonyms

17-ethinyl-3,17-estradiol
17-ethinyl-3,17-oestradiol
17-ethinylestradiol
17alpha-Ethinyl estradiol
17α-ethynylestradiol
Ethinyl estradiol
Ethinylestradiol
Ethinylestradiolum
Ethinyloestradiol
Ethynyl estradiol
Etinilestradiol

External IDs

NSC-10973

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Pharmacology

Indication

Ethinylestradiol is combined with other drugs for use as a contraceptive, premenstrual dysphoric disorder, moderate acne, moderate to severe vasomotor symptoms of menopause, prevention of postmenopausal osteoporosis.^{15,25,16,17,24,18,19,20,21,22,23}

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Used in combination to prevent	Menopausal osteoporosis	Combination Product in combination with: Norethisterone (DB00717)	••••••••••••	••••••••••		••••••
Used in combination to treat	Mild to moderate acne	Combination Product in combination with: Dienogest (DB09123)	••••••••••••		••••••• ••••••• •••• ••••••••••••• ••• ••••• •••••••	••••••
Used in combination to treat	Premenstrual dysphoric disorder (pmdd)	Combination Product in combination with: Drospirenone (DB01395)	••••••••••••			••••••
Used in combination to treat	Moderate acne vulgaris	Combination Product in combination with: Ferrous fumarate (DB14491), Norethisterone (DB00717)	••••••••••••			••••••
Used in combination to treat	Moderate acne vulgaris	Combination Product in combination with: Norgestimate (DB00957)	••••••••••••			••••••

Associated Therapies

Contraindications & Blackbox Warnings

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Pharmacodynamics

Ethinylestradiol is a synthetic estrogen that decreases luteinizing hormone to decrease endometrial vascularization, and decreases gonadotrophic hormone to prevent ovulation.^13,12,15 It has a long duration of action as it is taken once daily, and a wide therapeutic index as overdoses are generally not associated with serious adverse effects.¹⁵ Patients should be counselled regarding the risks of thrombotic events.¹⁵

Mechanism of action

Ethinylestradiol is a synthetic estrogenic compound.¹⁵ Use of estrogens have a number of effects on the body including reduced bone density.¹¹ Combined oral contraceptives suppress ovulation by suppressing gonadotrophic hormone, thickening cervical mucus to prevent the travel of sperm, and preventing changes in the endometrium required for implantation of a fertilized egg.^12,15 Ethinylestradiol decreases luteinizing hormone, decreasing vascularity in the endometrium.¹³ It also increases sex hormone binding globulin.¹³

Target	Actions	Organism
AEstrogen receptor alpha	agonist	Humans
UNuclear receptor subfamily 1 group I member 2	agonist	Humans

Absorption

A 30µg oral dose of ethinylestradiol reaches a C_max of 74.1±35.6pg/mL, with a T_max of 1.5±0.5h, and an AUC of 487.4±166.6pg*h/mL.¹⁰ A 1.2mg dose delivered via a patch reaches a C_max of 28.8±10.3pg/mL, with a T_max of 86±31h, and an AUC of3895±1423pg*h/mL.¹⁰

Volume of distribution

A 30µg oral dose has an apparent volume of distribution of 625.3±228.7L and a 1.2mg topical dose has an apparent volume of distribution of 11745.3±15934.8L.¹⁰

Protein binding

Enthinylestradiol is 98.3-98.5% bound to albumin in serum⁸ but also exhibits binding to sex hormone binding globulin.⁹

Metabolism

Ethinylestradiol can be glucuronidated by UGT1A1, UGT1A3, UGT1A4, UGT1A9, and UGT2B7.^3,7 Ethinylestradiol is also sulfated by SULT1A1, SULT1A3, and SULT1E1.^6,7 Ethinylestradiol can also be hydroxylated at positions 2, 4, 6, 7, and 16^5,7 by CYP3A4, CYP3A5, CYP2C8, CYP2C9, and CYP1A2.^4,7 These hydroxylated metabolites can be methylated by catechol-O-methyltransferase.⁷ The methoxy metabolites can in turn be sulfated or glucuronidated.⁷

Hover over products below to view reaction partners

Ethinylestradiol

Route of elimination

Ethinylestradiol is 59.2% eliminated in the urine and bile, while 2-3% is eliminated in the feces.² Over 90% of ethinylestradiol is eliminated as the unchanged parent drug.²

Half-life

A 30µg oral dose has a half life of 8.4±4.8h and a 1.2mg topical dose has a half life of 27.7±34.2h.¹⁰

Clearance

Ethinylestradiol has an intravenous clearance of 16.47L/h, and an estimated renal clearance of approximately 2.1L/h.⁴ A 30µg oral dose has a clearance of 58.0±19.8L/h and a 1.2mg topical dose has a clearance of 303.5±100.5L/h.¹⁰

Adverse Effects

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Toxicity

Female patients experiencing and overdose may present with withdrawal bleeding, nausea, vomiting, breast tenderness, abdominal pain, drowsiness, and fatigue.^{15,25,16,17,24,18,19,20,21,22,23} Overdose should be treated with symptomatic and supportive care including monitoring for potassium concentrations, sodium concentrations, and signs of metabolic acidosis.^{15,25,16,17,24,18,19,20,21,22,23}

Pathways

Not Available

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Interactions

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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.

Drug	Interaction
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Abacavir	The metabolism of Abacavir can be increased when combined with Ethinylestradiol.
Abametapir	The serum concentration of Ethinylestradiol can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Ethinylestradiol can be increased when combined with Abatacept.
Abciximab	The risk or severity of adverse effects can be increased when Ethinylestradiol is combined with Abciximab.
Abiraterone	The serum concentration of Ethinylestradiol can be increased when it is combined with Abiraterone.

Food Interactions

Avoid St. John's Wort. St. John's Wort may decrease the effectiveness of ethinylestradiol.

Products

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Active Moieties

Name	Kind	UNII	CAS	InChI Key
Estradiol	unknown	4TI98Z838E	50-28-2	VOXZDWNPVJITMN-ZBRFXRBCSA-N

Product Images

International/Other Brands

Estinyl (Schering)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Estinyl Tab 0.05mg	Tablet	.05 mg / tab	Oral	Schering Plough	1951-12-31	2000-07-11
Estinyl Tab 0.5mg	Tablet	.5 mg / tab	Oral	Schering Plough	1951-12-31	2000-07-11
Estinyl Tablets 0.02 Mg.	Tablet	.02 mg / tab	Oral	Schering Plough	1951-12-31	1998-11-17

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
ACTIVA 21	Ethinylestradiol (30 mcg) + Levonorgestrel (150 mcg)	Tablet, coated	Oral	FAES FARMA COLOMBIA S.A.S.	2008-04-10	Not applicable
ACTIVA 21 SUAVE®	Ethinylestradiol (20 mcg) + Levonorgestrel (100 mcg)	Tablet, coated	Oral	FAES FARMA COLOMBIA S.A.S.	2014-05-23	Not applicable
ADELLA MINI TABLETA CON RECUBRIMIENTO DE GELATINA	Ethinylestradiol (0.02 mg) + Chlormadinone (2 mg)	Tablet, coated	Oral	PROCAPS S.A.	2013-03-06	Not applicable
ADELLA®	Ethinylestradiol (0.03 mg) + Chlormadinone (2 mg)	Tablet, coated	Oral	PROCAPS S.A.	2013-04-03	Not applicable
Afirmelle	Ethinylestradiol (0.02 mg/1) + Levonorgestrel (0.1 mg/1)	Kit; Tablet	Oral	Aurobindo Pharma Limited	2016-11-14	Not applicable

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Falessa	Ethinylestradiol (0.02 mg/1) + Folic acid (1 mg/1) + Levonorgestrel (0.1 mg/1)	Kit	Oral	Avion Pharmaceuticals, Llc	2014-02-17	Not applicable
Mercilon	Ethinylestradiol (0.02 mg/1) + Desogestrel (0.15 mg/1)	Tablet	Oral	OASIS TRADING	2018-11-22	Not applicable
Minivlar 30	Ethinylestradiol (0.03 mg/1) + Levonorgestrel (0.15 mg/1)	Tablet	Oral	OASIS TRADING	2018-11-21	Not applicable
Myvlar	Ethinylestradiol (0.03 mg/1) + Gestodene (0.075 mg/1)	Tablet	Oral	OASIS TRADING	2018-11-22	Not applicable

Chemical Identifiers

UNII: 423D2T571U
CAS number: 57-63-6
InChI Key: BFPYWIDHMRZLRN-SLHNCBLASA-N
InChI: InChI=1S/C20H24O2/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/h1,5,7,12,16-18,21-22H,4,6,8-11H2,2H3/t16-,17-,18+,19+,20+/m1/s1
IUPAC Name: (1R,3aS,3bR,9bS,11aS)-1-ethynyl-11a-methyl-1H,2H,3H,3aH,3bH,4H,5H,9bH,10H,11H,11aH-cyclopenta[a]phenanthrene-1,7-diol
SMILES: [H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3

References

Synthesis Reference

Andreas Sachse, "Method of female hormonal contraception using a fixed extended cycle hormonal preparation containing dienogest and ethinyl estradiol." U.S. Patent US20060079491, issued April 13, 2006.

US20060079491

General References

Dhont M: History of oral contraception. Eur J Contracept Reprod Health Care. 2010 Dec;15 Suppl 2:S12-8. doi: 10.3109/13625187.2010.513071. [Article]
Cargill DI, Steinetz BG, Gosnell E, Beach VL, Meli A, Fujimoto GI, Reynolds BM: Fate of ingested radiolabeled ethynylestradiol and its 3-cyclopentyl ether in patients with bile fistulas. J Clin Endocrinol Metab. 1969 Aug;29(8):1051-61. doi: 10.1210/jcem-29-8-1051. [Article]
Ebner T, Remmel RP, Burchell B: Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol. Mol Pharmacol. 1993 Apr;43(4):649-54. [Article]
Ezuruike U, Humphries H, Dickins M, Neuhoff S, Gardner I, Rowland Yeo K: Risk-Benefit Assessment of Ethinylestradiol Using a Physiologically Based Pharmacokinetic Modeling Approach. Clin Pharmacol Ther. 2018 Dec;104(6):1229-1239. doi: 10.1002/cpt.1085. Epub 2018 Apr 27. [Article]
Bolt HM, Kappus H, Kasbohrer R: Metabolism of 17 alpha-ethinylestradiol by human liver microsomes in vitro: aromatic hydroxylation and irreversible protein binding of metabolites. J Clin Endocrinol Metab. 1974 Dec;39(6):1072-80. doi: 10.1210/jcem-39-6-1072. [Article]
Schrag ML, Cui D, Rushmore TH, Shou M, Ma B, Rodrigues AD: Sulfotransferase 1E1 is a low km isoform mediating the 3-O-sulfation of ethinyl estradiol. Drug Metab Dispos. 2004 Nov;32(11):1299-303. doi: 10.1124/dmd.32.11.. [Article]
Stegeman BH, Vos HL, Helmerhorst FM, Rosendaal FR, Reitsma PH, van Hylckama Vlieg A: Genetic variation in the first-pass metabolism of ethinylestradiol, sex hormone binding globulin levels and venous thrombosis risk. Eur J Intern Med. 2017 Jul;42:54-60. doi: 10.1016/j.ejim.2017.05.019. Epub 2017 Jun 1. [Article]
Kuhnz W, Pfeffer M, al-Yacoub G: Protein binding of the contraceptive steroids gestodene, 3-keto-desogestrel and ethinylestradiol in human serum. J Steroid Biochem. 1990 Feb;35(2):313-8. doi: 10.1016/0022-4731(90)90290-9. [Article]
Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W: Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and alpha-fetoprotein. Toxicol Sci. 2015 Feb;143(2):333-48. doi: 10.1093/toxsci/kfu231. Epub 2014 Oct 27. [Article]
Zhang C, Li H, Xiong X, Zhai S, Wei Y, Zhang S, Zhang Y, Xu L, Liu L: An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch. Drug Des Devel Ther. 2017 Mar 10;11:725-731. doi: 10.2147/DDDT.S131123. eCollection 2017. [Article]
Almstedt HC, Cook MM, Bramble LF, Dabir DV, LaBrie JW: Oral contraceptive use, bone mineral density, and bone turnover markers over 12 months in college-aged females. J Bone Miner Metab. 2020 Jan 25. pii: 10.1007/s00774-019-01081-1. doi: 10.1007/s00774-019-01081-1. [Article]
Regidor PA: Clinical relevance in present day hormonal contraception. Horm Mol Biol Clin Investig. 2018 Oct 26;37(1). pii: /j/hmbci.ahead-of-print/hmbci-2018-0030/hmbci-2018-0030.xml. doi: 10.1515/hmbci-2018-0030. [Article]
Sahu A, Tripathy P, Mohanty J, Nagy A: Doppler analysis of ovarian stromal blood flow changes after treatment with metformin versus ethinyl estradiol-cyproterone acetate in women with polycystic ovarian syndrome: A randomized controlled trial. J Gynecol Obstet Hum Reprod. 2019 May;48(5):335-339. doi: 10.1016/j.jogoh.2018.10.006. Epub 2018 Oct 11. [Article]
FDA Approved Drug Products: Estinyl Ethinylestradiol Oral Tablets (Discontinued) [Link]
FDA Approved Drug Products: Yaz Ethinylestradiol and Drospirenone Oral Tablets [Link]
FDA Approved Drug Products: Taytulla Ethinylestradiol and Norethindrone Acetate Oral Capsules and Ferrous Fumarate Oral Capsules [Link]
FDA Approved Drug Products: Safyral Ethinylestradiol, Drospirenons, and Levomefolate Calcium Oral Tablets and Levomefolate Oral Tablets [Link]
FDA Approved Drugs: Nuvaring® vaginal ring [Link]
FDA Approved Drug Products: Lo Ovral 28 Ethinylestradiol and Norgestrel Oral Tablets and Ferrous Fumarate Oral Tablets [Link]
FDA Approved Drug Products: Femhrt® tablets [Link]
FDA Approved Drug Products: Estrostep Fe Ethinylestradiol and Norethindrone Oral Tablets and Ferrous Fumarate Oral Tablets [Link]
FDA Approved Drug Products: Cyclessa Ethinylestradiol and Desogestrel Oral Tablets [Link]
FDA Approved Drug Products: Annovera Ethinylestradiol and Segesterone Acetate Vaginal System [Link]
FDA Approved Drug Products: Ortho Tri-Cyclen Norgestimate and Ethinyl Estradiol Oral Tablets [Link]
FDA Approved Drug Products: Seasonale Ethinylestradiol and Levonorgestrel Oral Tablets [Link]
FDA Approved Drug Products: LOSEASONIQUE® (levonorgestrel and ethinyl estradiol tablets; and ethinyl estradiol tablets) for oral use [Link]

External Links

Human Metabolome Database: HMDB0001926
KEGG Drug: D00554
KEGG Compound: C07534
PubChem Compound: 5991
PubChem Substance: 46508618
ChemSpider: 5770
BindingDB: 50187243
RxNav: 4124
ChEBI: 4903
ChEMBL: CHEMBL691
ZINC: ZINC000003812897
Therapeutic Targets Database: DAP001018
PharmGKB: PA449527
PDBe Ligand: 3WF
RxList: RxList Drug Page
Wikipedia: Ethinylestradiol

PDB Entries

4x1f / 4x1g

FDA label

Download (470 KB)

MSDS

Download (73.9 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Basic Science	Other Disorders of Bone Development and Growth	1
4	Completed	Not Available	Polycystic Ovarian Syndrome (PCOS)	1
4	Completed	Basic Science	Adverse Effect of Oral Contraceptives, Subsequent Encounter	1
4	Completed	Basic Science	Bone; Disorder, Development and Growth	1
4	Completed	Basic Science	Contraception	3

Pharmacoeconomics

Manufacturers

Schering corp sub schering plough corp
Pharmacia and upjohn co
Organon usa inc

Packagers

Amerisource Health Services Corp.
Barr Pharmaceuticals
Bayer Healthcare
Dept Health Central Pharmacy
Duramed
Mckesson Corp.
NV Organon
Organon Pharmaceuticals
Ortho Mcneil Janssen Pharmaceutical Inc.
Ortho-McNeil-Janssen Pharmaceuticals Inc.
Pharmaceutical Utilization Management Program VA Inc.
Physicians Total Care Inc.
Prasco Labs
Schering Corp.
Spectrum Pharmaceuticals
Teva Pharmaceutical Industries Ltd.
Watson Pharmaceuticals

Dosage Forms

Form	Route	Strength
Kit; tablet	Oral
Ring	Vaginal
Tablet, film coated	Oral	15 MCG
Tablet, film coated	Oral	2.000 mg
Kit	Oral
Tablet, delayed release	Oral
Tablet, film coated		0.03 MG/3MG
Kit; tablet, film coated	Oral
Tablet, film coated	Oral	2 MG
Tablet, coated	Oral	0.02 MG
Tablet	Oral	.05 mg / tab
Tablet	Oral	.5 mg / tab
Tablet	Oral	.02 mg / tab
Tablet, film coated	Oral	0.03 MG
Tablet, delayed release	Oral	10 MICROGRAMMI
Tablet, delayed release	Oral	100 MICROGRAMMI
Tablet, delayed release	Oral	1000 MICROGRAMMI
Tablet, delayed release	Oral	50 MICROGRAMMI
Tablet, sugar coated	Oral
Patch	Transdermal	600 mcg
Patch	Transdermal	6 mg
Solution	Transdermal
Tablet	Oral
Tablet, chewable	Oral
Tablet, coated	Oral
Tablet	Oral	20.000 mcg
Solution	Oral
Kit; tablet, chewable	Oral
Tablet	Oral	3.000 mg
Kit; tablet; tablet, chewable	Oral
Tablet	Oral	0.150 mg
Tablet, film coated	Oral
Tablet, sugar coated	Oral	0.02 mg
Tablet, sugar coated	Oral	0.03 mg
Tablet, film coated		0.03 MG/2MG
Drug delivery system	Vaginal
Insert, extended release	Vaginal
Patch, extended release	Transdermal
Tablet, film coated		0.02 MG/3MG
Tablet, film coated; tablet, sugar coated	Oral
Kit; tablet, coated	Oral
Capsule, liquid filled; kit	Oral
Capsule, liquid filled	Oral
Patch	Transdermal
Tablet, film coated	Oral	3 mg
Tablet, film coated	Oral	0.02 MG
Tablet, film coated
Tablet
Tablet, film coated

Prices

Unit description	Cost	Unit
Ethinyl estradiol powder	140.0USD	g
Ortho-Cyclen (28) 28 0.25-35 mg-mcg tablet Disp Pack	38.99USD	disp
Ortho tri-cyclen lo tablet	2.68USD	tablet
Ortho-cyclen 28 tablet	1.13USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US6156742	No	2000-12-05	2020-12-05
US6787531	No	2004-09-07	2020-08-31
US6933395	No	2005-08-23	2017-08-11
US5876746	No	1999-03-02	2015-11-20
US5989581	No	1999-11-23	2018-04-08
US6214815	Yes	2001-04-10	2019-12-09
US6667050	No	2003-12-23	2019-04-06
US5898032	No	1999-04-27	2017-06-23
USRE39861	No	2007-09-25	2017-06-23
US6987101	No	2006-01-17	2017-12-22
US7163931	No	2007-01-16	2021-12-20
US6958326	No	2005-10-25	2021-12-20
US5798338	No	1998-08-25	2015-07-10
US7320969	No	2008-01-22	2024-01-30
US7615545	No	2009-11-10	2023-06-15
US7855190	No	2010-12-21	2028-12-05
US7858605	No	2010-12-28	2023-06-23
US6500814	No	2002-12-31	2018-09-03
US7704984	No	2010-04-27	2029-02-02
US6441168	No	2002-08-27	2022-07-30
US8617597	No	2013-12-31	2030-02-08
US8450299	No	2013-05-28	2025-10-07
US8415332	No	2013-04-09	2029-03-11
US6652880	No	2003-11-25	2020-03-29
US6716814	No	2004-04-06	2021-08-16
US9050348	No	2015-06-09	2028-07-10
US8221784	No	2012-07-17	2021-03-14
US8747888	No	2014-06-10	2028-07-10
US8221785	No	2012-07-17	2021-03-14
US7384650	No	2008-06-10	2021-03-14
US8246978	No	2012-08-21	2028-08-26
US8883196	No	2014-11-11	2020-11-22
US7045145	No	2006-05-16	2021-03-14
US10632066	No	2020-04-28	2039-02-01
US10780047	No	2020-09-22	2039-02-01
US10765628	No	2020-09-08	2039-02-01
US10918649	No	2021-02-16	2039-06-21
US10925882	No	2021-02-23	2039-06-21
US10940157	No	2021-03-09	2039-06-21
US7838042	No	2010-11-23	2027-06-01
US11529308	No	2019-06-21	2039-06-21
US11617751	No	2010-07-17	2030-07-17

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	142-144	Inhoffen, H.H. and Hohlweg, W.; U.S. Patent 2,265,976; December 9, 1941; assigned to Schering Corp.
water solubility	11.3 mg/L (at 27 °C)	YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP	3.67	HANSCH,C ET AL. (1995)
logS	-4.3	ADME Research, USCD

Predicted Properties

Property	Value	Source
Water Solubility	0.00677 mg/mL	ALOGPS
logP	3.63	ALOGPS
logP	3.9	Chemaxon
logS	-4.6	ALOGPS
pKa (Strongest Acidic)	10.33	Chemaxon
pKa (Strongest Basic)	-1.7	Chemaxon
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	2	Chemaxon
Hydrogen Donor Count	2	Chemaxon
Polar Surface Area	40.46 Å²	Chemaxon
Rotatable Bond Count	0	Chemaxon
Refractivity	87.37 m³·mol^-1	Chemaxon
Polarizability	34.53 Å³	Chemaxon
Number of Rings	4	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.9965
Blood Brain Barrier	+	0.8546
Caco-2 permeable	+	0.8638
P-glycoprotein substrate	Substrate	0.6892
P-glycoprotein inhibitor I	Non-inhibitor	0.9006
P-glycoprotein inhibitor II	Non-inhibitor	0.9449
Renal organic cation transporter	Non-inhibitor	0.84
CYP450 2C9 substrate	Non-substrate	0.7178
CYP450 2D6 substrate	Non-substrate	0.9116
CYP450 3A4 substrate	Substrate	0.715
CYP450 1A2 substrate	Inhibitor	0.8941
CYP450 2C9 inhibitor	Non-inhibitor	0.9186
CYP450 2D6 inhibitor	Non-inhibitor	0.9506
CYP450 2C19 inhibitor	Non-inhibitor	0.6641
CYP450 3A4 inhibitor	Inhibitor	0.5224
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.6776
Ames test	Non AMES toxic	0.9155
Carcinogenicity	Non-carcinogens	0.8519
Biodegradation	Not ready biodegradable	0.9879
Rat acute toxicity	2.4584 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.8805
hERG inhibition (predictor II)	Inhibitor	0.5788

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Download (9.42 KB)

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	splash10-06ec-0890000000-23c55dc07e698aa701e4
GC-MS Spectrum - EI-B	GC-MS	splash10-03di-0890000000-5219bc8ac1212313c9c0
Mass Spectrum (Electron Ionization)	MS	splash10-03dj-2980000000-831c8190c59f98fc8623
MS/MS Spectrum - Quattro_QQQ 10V, Positive	LC-MS/MS	splash10-000b-0290000000-0ef72fb5e00440b9ff50
MS/MS Spectrum - Quattro_QQQ 25V, Positive	LC-MS/MS	splash10-000i-0960000000-945d82a0ab94f246ac88
MS/MS Spectrum - Quattro_QQQ 40V, Positive	LC-MS/MS	splash10-056s-2910000000-0d38daebb87a39304e91
MS/MS Spectrum - EI-B (HITACHI M-80) , Positive	LC-MS/MS	splash10-03di-0890000000-7a166e952207cf7bc1d3
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0002-0090000000-cfd3dbc71d3bb6140b0d
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0002-0090000000-8dd2522a15ebe1619dc8
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-004i-0390000000-bcc5f09f7efce65d6c21
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0002-0090000000-75e96be47865cccaba36
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-01b9-0890000000-cf86fd77d6b2ce6ad6bb
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0uka-0910000000-4d27f79ada68d98becb4
1H NMR Spectrum	1D NMR	Not Applicable
13C NMR Spectrum	1D NMR	Not Applicable
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable
[1H,13C] 2D NMR Spectrum	2D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	180.8060476	predicted	DarkChem Lite v0.1.0
[M-H]-	170.5988603	predicted	DarkChem Lite v0.1.0
[M-H]-	181.5281476	predicted	DarkChem Lite v0.1.0
[M-H]-	181.5711476	predicted	DarkChem Lite v0.1.0
[M-H]-	180.6093	predicted	DeepCCS 1.0 (2019)
[M+H]+	180.1968476	predicted	DarkChem Lite v0.1.0
[M+H]+	174.6208244	predicted	DarkChem Lite v0.1.0
[M+H]+	179.5511476	predicted	DarkChem Lite v0.1.0
[M+H]+	179.9237476	predicted	DarkChem Lite v0.1.0
[M+H]+	182.71953	predicted	DeepCCS 1.0 (2019)
[M+Na]+	180.3334476	predicted	DarkChem Lite v0.1.0
[M+Na]+	185.0644334	predicted	DarkChem Lite v0.1.0
[M+Na]+	179.1851476	predicted	DarkChem Lite v0.1.0
[M+Na]+	178.4804476	predicted	DarkChem Lite v0.1.0
[M+Na]+	188.63206	predicted	DeepCCS 1.0 (2019)

Targets

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Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	2	N/A	N/A	A28359

Details1. Estrogen receptor alpha

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Agonist

General Function: Zinc ion binding
Specific Function: Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
Gene Name: ESR1
Uniprot ID: P03372
Uniprot Name: Estrogen receptor
Molecular Weight: 66215.45 Da

References

Micevych PE, Chaban V, Ogi J, Dewing P, Lu JK, Sinchak K: Estradiol stimulates progesterone synthesis in hypothalamic astrocyte cultures. Endocrinology. 2007 Feb;148(2):782-9. Epub 2006 Nov 9. [Article]
Garcia-Segura LM, Sanz A, Mendez P: Cross-talk between IGF-I and estradiol in the brain: focus on neuroprotection. Neuroendocrinology. 2006;84(4):275-9. Epub 2006 Nov 23. [Article]
Brama M, Gnessi L, Basciani S, Cerulli N, Politi L, Spera G, Mariani S, Cherubini S, Scotto d'Abusco A, Scandurra R, Migliaccio S: Cadmium induces mitogenic signaling in breast cancer cell by an ERalpha-dependent mechanism. Mol Cell Endocrinol. 2007 Jan 29;264(1-2):102-8. Epub 2006 Nov 27. [Article]
Lehnes K, Winder AD, Alfonso C, Kasid N, Simoneaux M, Summe H, Morgan E, Iann MC, Duncan J, Eagan M, Tavaluc R, Evans CH Jr, Russell R, Wang A, Hu F, Stoica A: The effect of estradiol on in vivo tumorigenesis is modulated by the human epidermal growth factor receptor 2/phosphatidylinositol 3-kinase/Akt1 pathway. Endocrinology. 2007 Mar;148(3):1171-80. Epub 2006 Nov 30. [Article]
Mukai H, Tsurugizawa T, Ogiue-Ikeda M, Murakami G, Hojo Y, Ishii H, Kimoto T, Kawato S: Local neurosteroid production in the hippocampus: influence on synaptic plasticity of memory. Neuroendocrinology. 2006;84(4):255-63. Epub 2006 Dec 1. [Article]
Notch EG, Mayer GD: 17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Dec 13;95(4):273-8. doi: 10.1016/j.aquatox.2009.01.001. Epub 2009 Jan 23. [Article]
Bennink HJ: Reprint of Are all estrogens the same? Maturitas. 2008 Sep-Oct;61(1-2):195-201. [Article]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Details2. Nuclear receptor subfamily 1 group I member 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Agonist

General Function: Zinc ion binding
Specific Function: Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name: NR1I2
Uniprot ID: O75469
Uniprot Name: Nuclear receptor subfamily 1 group I member 2
Molecular Weight: 49761.245 Da

References

Xue Y, Moore LB, Orans J, Peng L, Bencharit S, Kliewer SA, Redinbo MR: Crystal structure of the pregnane X receptor-estradiol complex provides insights into endobiotic recognition. Mol Endocrinol. 2007 May;21(5):1028-38. Epub 2007 Feb 27. [Article]

Enzymes

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	18000	N/A	N/A	A18342

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
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 react...
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Wang B, Sanchez RI, Franklin RB, Evans DC, Huskey SE: The involvement of CYP3A4 and CYP2C9 in the metabolism of 17 alpha-ethinylestradiol. Drug Metab Dispos. 2004 Nov;32(11):1209-12. Epub 2004 Aug 10. [Article]
Ezuruike U, Humphries H, Dickins M, Neuhoff S, Gardner I, Rowland Yeo K: Risk-Benefit Assessment of Ethinylestradiol Using a Physiologically Based Pharmacokinetic Modeling Approach. Clin Pharmacol Ther. 2018 Dec;104(6):1229-1239. doi: 10.1002/cpt.1085. Epub 2018 Apr 27. [Article]

Details2. Cytochrome P450 2C8

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
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

Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [Article]
Ezuruike U, Humphries H, Dickins M, Neuhoff S, Gardner I, Rowland Yeo K: Risk-Benefit Assessment of Ethinylestradiol Using a Physiologically Based Pharmacokinetic Modeling Approach. Clin Pharmacol Ther. 2018 Dec;104(6):1229-1239. doi: 10.1002/cpt.1085. Epub 2018 Apr 27. [Article]

Details3. Cytochrome P450 2C9

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

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

Ezuruike U, Humphries H, Dickins M, Neuhoff S, Gardner I, Rowland Yeo K: Risk-Benefit Assessment of Ethinylestradiol Using a Physiologically Based Pharmacokinetic Modeling Approach. Clin Pharmacol Ther. 2018 Dec;104(6):1229-1239. doi: 10.1002/cpt.1085. Epub 2018 Apr 27. [Article]

Details4. Cytochrome P450 1A2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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: CYP1A2
Uniprot ID: P05177
Uniprot Name: Cytochrome P450 1A2
Molecular Weight: 58293.76 Da

References

Ezuruike U, Humphries H, Dickins M, Neuhoff S, Gardner I, Rowland Yeo K: Risk-Benefit Assessment of Ethinylestradiol Using a Physiologically Based Pharmacokinetic Modeling Approach. Clin Pharmacol Ther. 2018 Dec;104(6):1229-1239. doi: 10.1002/cpt.1085. Epub 2018 Apr 27. [Article]

Details5. Cytochrome P450 3A5

Kind: Protein
Organism: Humans
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 un...
Gene Name: CYP3A5
Uniprot ID: P20815
Uniprot Name: Cytochrome P450 3A5
Molecular Weight: 57108.065 Da

References

Stegeman BH, Vos HL, Helmerhorst FM, Rosendaal FR, Reitsma PH, van Hylckama Vlieg A: Genetic variation in the first-pass metabolism of ethinylestradiol, sex hormone binding globulin levels and venous thrombosis risk. Eur J Intern Med. 2017 Jul;42:54-60. doi: 10.1016/j.ejim.2017.05.019. Epub 2017 Jun 1. [Article]

Details6. UDP-glucuronosyltransferase 1-4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Protein homodimerization activity
Specific Function: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name: UGT1A4
Uniprot ID: P22310
Uniprot Name: UDP-glucuronosyltransferase 1-4
Molecular Weight: 60024.535 Da

References

Ebner T, Remmel RP, Burchell B: Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol. Mol Pharmacol. 1993 Apr;43(4):649-54. [Article]

Details7. UDP-glucuronosyltransferase 1-3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Retinoic acid binding
Specific Function: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name: UGT1A3
Uniprot ID: P35503
Uniprot Name: UDP-glucuronosyltransferase 1-3
Molecular Weight: 60337.835 Da

References

Stegeman BH, Vos HL, Helmerhorst FM, Rosendaal FR, Reitsma PH, van Hylckama Vlieg A: Genetic variation in the first-pass metabolism of ethinylestradiol, sex hormone binding globulin levels and venous thrombosis risk. Eur J Intern Med. 2017 Jul;42:54-60. doi: 10.1016/j.ejim.2017.05.019. Epub 2017 Jun 1. [Article]

Details8. UDP-glucuronosyltransferase 1-1

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate
Inducer

General Function: Steroid binding
Specific Function: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name: UGT1A1
Uniprot ID: P22309
Uniprot Name: UDP-glucuronosyltransferase 1-1
Molecular Weight: 59590.91 Da

References

Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [Article]
Ezuruike U, Humphries H, Dickins M, Neuhoff S, Gardner I, Rowland Yeo K: Risk-Benefit Assessment of Ethinylestradiol Using a Physiologically Based Pharmacokinetic Modeling Approach. Clin Pharmacol Ther. 2018 Dec;104(6):1229-1239. doi: 10.1002/cpt.1085. Epub 2018 Apr 27. [Article]
Rohn-Glowacki KJ, Falany CN: The potent inhibition of human cytosolic sulfotransferase 1A1 by 17alpha-ethinylestradiol is due to interactions with isoleucine 89 on loop 1. Horm Mol Biol Clin Investig. 2014 Dec;20(3):81-90. doi: 10.1515/hmbci-2014-0028. [Article]
Ebner T, Remmel RP, Burchell B: Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol. Mol Pharmacol. 1993 Apr;43(4):649-54. [Article]

Details9. UDP-glucuronosyltransferase 1-9

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Retinoic acid binding
Specific Function: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name: UGT1A9
Uniprot ID: O60656
Uniprot Name: UDP-glucuronosyltransferase 1-9
Molecular Weight: 59940.495 Da

References

Ebner T, Remmel RP, Burchell B: Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol. Mol Pharmacol. 1993 Apr;43(4):649-54. [Article]

Details10. UDP-glucuronosyltransferase 2B7

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Glucuronosyltransferase activity
Specific Function: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name: UGT2B7
Uniprot ID: P16662
Uniprot Name: UDP-glucuronosyltransferase 2B7
Molecular Weight: 60694.12 Da

References

Stegeman BH, Vos HL, Helmerhorst FM, Rosendaal FR, Reitsma PH, van Hylckama Vlieg A: Genetic variation in the first-pass metabolism of ethinylestradiol, sex hormone binding globulin levels and venous thrombosis risk. Eur J Intern Med. 2017 Jul;42:54-60. doi: 10.1016/j.ejim.2017.05.019. Epub 2017 Jun 1. [Article]

Details11. Sulfotransferase 1A3/1A4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of phenolic monoamines (neurotransmitters such as dopamine, norepinephrine and serotonin) and phenolic and catechol drugs.
Specific Function: Amine sulfotransferase activity
Gene Name: SULT1A3
Uniprot ID: P0DMM9
Uniprot Name: Sulfotransferase 1A3
Molecular Weight: 34195.96 Da

References

Schrag ML, Cui D, Rushmore TH, Shou M, Ma B, Rodrigues AD: Sulfotransferase 1E1 is a low km isoform mediating the 3-O-sulfation of ethinyl estradiol. Drug Metab Dispos. 2004 Nov;32(11):1299-303. doi: 10.1124/dmd.32.11.. [Article]

Details12. Estrogen sulfotransferase

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Sulfotransferase activity
Specific Function: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of estradiol and estrone. May play a role in the regulation of estrogen r...
Gene Name: SULT1E1
Uniprot ID: P49888
Uniprot Name: Estrogen sulfotransferase
Molecular Weight: 35126.185 Da

References

Schrag ML, Cui D, Rushmore TH, Shou M, Ma B, Rodrigues AD: Sulfotransferase 1E1 is a low km isoform mediating the 3-O-sulfation of ethinyl estradiol. Drug Metab Dispos. 2004 Nov;32(11):1299-303. doi: 10.1124/dmd.32.11.. [Article]

Details13. Catechol O-methyltransferase

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: O-methyltransferase activity
Specific Function: Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOP...
Gene Name: COMT
Uniprot ID: P21964
Uniprot Name: Catechol O-methyltransferase
Molecular Weight: 30036.77 Da

References

Stegeman BH, Vos HL, Helmerhorst FM, Rosendaal FR, Reitsma PH, van Hylckama Vlieg A: Genetic variation in the first-pass metabolism of ethinylestradiol, sex hormone binding globulin levels and venous thrombosis risk. Eur J Intern Med. 2017 Jul;42:54-60. doi: 10.1016/j.ejim.2017.05.019. Epub 2017 Jun 1. [Article]

Details14. Cytochrome P450 2C19

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

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

Pedersen RS, Noehr-Jensen L, Brosen K: Inhibitory effect of oral contraceptives on CYP2C19 activity is not significant in carriers of the CYP2C19*17 allele. Clin Exp Pharmacol Physiol. 2013 Oct;40(10):683-8. doi: 10.1111/1440-1681.12153. [Article]
Palovaara S, Tybring G, Laine K: The effect of ethinyloestradiol and levonorgestrel on the CYP2C19-mediated metabolism of omeprazole in healthy female subjects. Br J Clin Pharmacol. 2003 Aug;56(2):232-7. doi: 10.1046/j.1365-2125.2003.01868.x. [Article]
Chang SY, Chen C, Yang Z, Rodrigues AD: Further assessment of 17alpha-ethinyl estradiol as an inhibitor of different human cytochrome P450 forms in vitro. Drug Metab Dispos. 2009 Aug;37(8):1667-75. doi: 10.1124/dmd.109.026997. Epub 2009 May 19. [Article]

Carriers

Details1. Serum albumin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
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

Kuhnz W, Pfeffer M, al-Yacoub G: Protein binding of the contraceptive steroids gestodene, 3-keto-desogestrel and ethinylestradiol in human serum. J Steroid Biochem. 1990 Feb;35(2):313-8. doi: 10.1016/0022-4731(90)90290-9. [Article]

Details2. Sex hormone-binding globulin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Binder

General Function: Androgen binding
Specific Function: Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
Gene Name: SHBG
Uniprot ID: P04278
Uniprot Name: Sex hormone-binding globulin
Molecular Weight: 43778.755 Da

References

Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W: Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and alpha-fetoprotein. Toxicol Sci. 2015 Feb;143(2):333-48. doi: 10.1093/toxsci/kfu231. Epub 2014 Oct 27. [Article]

Transporters

Details1. Bile salt export pump

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor
Curator comments: Estradiol trans-inhibits BSEP only after its secretion into bile canaliculi by Mrp2.

General Function: Transporter activity
Specific Function: Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name: ABCB11
Uniprot ID: O95342
Uniprot Name: Bile salt export pump
Molecular Weight: 146405.83 Da

References

Lee JM, Trauner M, Soroka CJ, Stieger B, Meier PJ, Boyer JL: Expression of the bile salt export pump is maintained after chronic cholestasis in the rat. Gastroenterology. 2000 Jan;118(1):163-72. [Article]
Huang L, Smit JW, Meijer DK, Vore M: Mrp2 is essential for estradiol-17beta(beta-D-glucuronide)-induced cholestasis in rats. Hepatology. 2000 Jul;32(1):66-72. [Article]
Stieger B, Fattinger K, Madon J, Kullak-Ublick GA, Meier PJ: Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology. 2000 Feb;118(2):422-30. [Article]

Details2. Sodium/bile acid cotransporter

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Virus receptor activity
Specific Function: The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presenc...
Gene Name: SLC10A1
Uniprot ID: Q14973
Uniprot Name: Sodium/bile acid cotransporter
Molecular Weight: 38118.64 Da

References

Lee JM, Trauner M, Soroka CJ, Stieger B, Meier PJ, Boyer JL: Expression of the bile salt export pump is maintained after chronic cholestasis in the rat. Gastroenterology. 2000 Jan;118(1):163-72. [Article]

Details3. Canalicular multispecific organic anion transporter 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor
Inducer
Curator comments: This transporter is induced at low concentrations of ethinylestradiol and inhibited at higher concentrations.

General Function: Organic anion transmembrane transporter activity
Specific Function: Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name: ABCC2
Uniprot ID: Q92887
Uniprot Name: Canalicular multispecific organic anion transporter 1
Molecular Weight: 174205.64 Da

References

Kauffmann HM, Schrenk D: Sequence analysis and functional characterization of the 5'-flanking region of the rat multidrug resistance protein 2 (mrp2) gene. Biochem Biophys Res Commun. 1998 Apr 17;245(2):325-31. [Article]
Trauner M, Arrese M, Soroka CJ, Ananthanarayanan M, Koeppel TA, Schlosser SF, Suchy FJ, Keppler D, Boyer JL: The rat canalicular conjugate export pump (Mrp2) is down-regulated in intrahepatic and obstructive cholestasis. Gastroenterology. 1997 Jul;113(1):255-64. [Article]

Details4. P-glycoprotein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

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

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. [Article]
Huang L, Smit JW, Meijer DK, Vore M: Mrp2 is essential for estradiol-17beta(beta-D-glucuronide)-induced cholestasis in rats. Hepatology. 2000 Jul;32(1):66-72. [Article]

Details5. Solute carrier organic anion transporter family member 1A2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Sodium-independent organic anion transmembrane transporter activity
Specific Function: Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name: SLCO1A2
Uniprot ID: P46721
Uniprot Name: Solute carrier organic anion transporter family member 1A2
Molecular Weight: 74144.105 Da

References

Lee JM, Trauner M, Soroka CJ, Stieger B, Meier PJ, Boyer JL: Expression of the bile salt export pump is maintained after chronic cholestasis in the rat. Gastroenterology. 2000 Jan;118(1):163-72. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55

Ethinylestradiol

Identification

Structure for Ethinylestradiol (DB00977)

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Properties

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Enzymes

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Carriers

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Transporters

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