Identification

Name
Desogestrel
Accession Number
DB00304  (APRD00762)
Type
Small Molecule
Groups
Approved
Description

A synthetic progestational hormone used often as the progestogenic component of combined oral contraceptive agents.

Structure
Thumb
Synonyms
  • 13-Ethyl-11-methylene-18,19-dinor-17alpha-pregn-4-en-20-yn-17-ol
  • Desogestrelum
External IDs
ORG 2969
Product Images
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
ApriDesogestrel (0.15 mg/1) + Ethinylestradiol (0.03 mg/1)KitA-S Medication Solutions1999-10-22Not applicableUs
ApriDesogestrel (0.15 mg/1) + Ethinylestradiol (0.03 mg/1)KitPhysicians Total Care, Inc.2003-03-10Not applicableUs54868 475420180907 15195 183ataj
Apri 21Desogestrel (0.15 mg) + Ethinylestradiol (0.03 mg)TabletOralTeva2008-09-29Not applicableCanada
Apri 28Desogestrel (0.15 mg) + Ethinylestradiol (0.03 mg)TabletOralTeva2008-09-29Not applicableCanada
Apri 28 DayDesogestrel (0.15 mg/1) + Ethinylestradiol (0.03 mg/1)KitTeva1999-10-22Not applicableUs00555 9043 58 nlmimage10 d5136aab
AzuretteDesogestrel (0.15 mg/1) + Ethinylestradiol (0.02 mg/1)KitRpk Pharmaceuticals, Inc.2016-11-14Not applicableUs
AzuretteDesogestrel (0.15 mg/1) + Ethinylestradiol (0.02 mg/1) + Ethinylestradiol (0.01 mg/1)KitActavis Pharma Company2008-12-302017-12-31Us52544 0940 28 nlmimage10 ad3ad6f6
AzuretteDesogestrel (0.15 mg/1) + Ethinylestradiol (0.02 mg/1) + Ethinylestradiol (0.01 mg/1)KitMayne Pharma2016-11-14Not applicableUs
BekyreeDesogestrel (0.15 mg/1) + Ethinylestradiol (0.02 mg/1) + Ethinylestradiol (0.01 mg/1)KitLupin Pharmaceuticals2018-01-20Not applicableUs
BekyreeDesogestrel (0.15 mg/1) + Ethinylestradiol (0.02 mg/1) + Ethinylestradiol (0.01 mg/1)KitLupin Pharmaceuticals2015-10-26Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
CesiaDesogestrel (0.1 mg/1) + Desogestrel (0.125 mg/1) + Desogestrel (0.15 mg/1) + Ethinylestradiol (0.025 mg/1) + Ethinylestradiol (0.025 mg/1) + Ethinylestradiol (0.025 mg/1)KitPrasco, Laboratories2009-02-17Not applicableUs
CesiaDesogestrel (0.1 mg/1) + Desogestrel (0.125 mg/1) + Desogestrel (0.15 mg/1) + Ethinylestradiol (0.025 mg/1) + Ethinylestradiol (0.025 mg/1) + Ethinylestradiol (0.025 mg/1)KitPrasco, Laboratories2009-02-17Not applicableUs
CesiaDesogestrel (0.1 mg/1) + Desogestrel (0.125 mg/1) + Desogestrel (0.15 mg/1) + Ethinylestradiol (0.025 mg/1) + Ethinylestradiol (0.025 mg/1) + Ethinylestradiol (0.025 mg/1)KitPrasco, Laboratories2009-02-17Not applicableUs
International/Other Brands
Cerazette (Organon) / Marvelon (Adcock Ingram Pharmaceuticals)
Categories
UNII
81K9V7M3A3
CAS number
54024-22-5
Weight
Average: 310.473
Monoisotopic: 310.229665582
Chemical Formula
C22H30O
InChI Key
RPLCPCMSCLEKRS-BPIQYHPVSA-N
InChI
InChI=1S/C22H30O/c1-4-21-14-15(3)20-17-9-7-6-8-16(17)10-11-18(20)19(21)12-13-22(21,23)5-2/h2,8,17-20,23H,3-4,6-7,9-14H2,1H3/t17-,18-,19-,20+,21-,22-/m0/s1
IUPAC Name
(1S,2R,10S,11S,14R,15S)-15-ethyl-14-ethynyl-17-methylidenetetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-14-ol
SMILES
[H][C@@]12CC[C@@](O)(C#C)[C@@]1(CC)CC(=C)[C@]1([H])[C@@]3([H])CCCC=C3CC[C@@]21[H]

Pharmacology

Indication

For the prevention of pregnancy in women who elect to use this product as a method of contraception.

Associated Therapies
Pharmacodynamics

Desogestrel is used as a female contraceptive. Desogestrel is a progestin or a synthetic form of the naturally occurring female sex hormone, progesterone. In a woman's normal menstrual cycle, an egg matures and is released from the ovaries (ovulation). The ovary then produces progesterone, preventing the release of further eggs and priming the lining of the womb for a possible pregnancy. If pregnancy occurs, progesterone levels in the body remain high, maintaining the womb lining. If pregnancy does not occur, progesterone levels in the body fall, resulting in a menstrual period. Desogestrel tricks the body processes into thinking that ovulation has already occurred, by maintaining high levels of the synthetic progesterone. This prevents the release of eggs from the ovaries.

Mechanism of action

Binds to the progesterone and estrogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like desogestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge.

TargetActionsOrganism
AProgesterone receptor
agonist
Human
AEstrogen receptor alpha
agonist
Human
Absorption

Following oral administration, the relative bioavailability of desogestrel, as measured by serum levels of etonogestrel, is approximately 84%. The absolute oral bioavailability is about 76%.

Volume of distribution
Not Available
Protein binding

98.3%

Metabolism

Desogestrel is rapidly and completely metabolized by hydroxylation in the intestinal mucosa and on first pass through the liver. It is primarily metabolized to 3α-hydroxydesogestrel with small amounts of 3β-hydroxydesogestrel being formed. Both of these metabolites are then rapidly oxidized to its active metabolite, etonogestrel (3-ketodesogestrel). Other metabolites (e.g. 2-hydroxydesogestrel) with no pharmacologic action have also been identified. Desogestrel and some of its metabolites (e.g. 3β-hydroxydesogestrel, 15β-hydroxydesogestrel) may also undergo glucuronide and sulfate conjugation. Early in vitro studies demonstrated that CYP2C9 and possibly CYP2C19 were involved in the conversion of desogestrel to 3α-hydroxydesogestrel and 3β-hydroxydesogestrel (PMID 9864282); however, later clinical studies conducted in humans refuted this result (PMID 15963096). The latter study indicates that CYP3A4 plays an important role in metabolizing etonogestrel. Thus, strong CYP3A4 inhibitors or inducers could result in increased side effects or therapeutic failure, respectively.

Route of elimination
Not Available
Half life

27.8±7.2 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include nausea and vaginal bleeding.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe therapeutic efficacy of (R)-warfarin can be increased when used in combination with Desogestrel.
(S)-WarfarinThe therapeutic efficacy of (S)-Warfarin can be increased when used in combination with Desogestrel.
16-BromoepiandrosteroneThe metabolism of 16-Bromoepiandrosterone can be decreased when combined with Desogestrel.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Desogestrel.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Desogestrel.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Desogestrel.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Desogestrel.
6-Deoxyerythronolide BThe metabolism of Desogestrel can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Desogestrel.
AbciximabThe therapeutic efficacy of Abciximab can be increased when used in combination with Desogestrel.
Food Interactions
Not Available

References

Synthesis Reference

Klaus Nickisch, "METHODS FOR THE PREPARATION OF ETONOGESTREL AND DESOGESTREL." U.S. Patent US20130123523, issued May 16, 2013.

US20130123523
General References
  1. Korhonen T, Tolonen A, Uusitalo J, Lundgren S, Jalonen J, Laine K: The role of CYP2C and CYP3A in the disposition of 3-keto-desogestrel after administration of desogestrel. Br J Clin Pharmacol. 2005 Jul;60(1):69-75. [PubMed:15963096]
  2. Gentile DM, Verhoeven CH, Shimada T, Back DJ: The role of CYP2C in the in vitro bioactivation of the contraceptive steroid desogestrel. J Pharmacol Exp Ther. 1998 Dec;287(3):975-82. [PubMed:9864282]
External Links
Human Metabolome Database
HMDB0014449
KEGG Drug
D02367
KEGG Compound
C07629
PubChem Compound
40973
PubChem Substance
46505739
ChemSpider
37400
BindingDB
50423510
ChEBI
4453
ChEMBL
CHEMBL1533
Therapeutic Targets Database
DAP001209
PharmGKB
PA449238
RxList
RxList Drug Page
Wikipedia
Desogestrel
ATC Codes
G03AC09 — DesogestrelG03AA09 — Desogestrel and ethinylestradiolG03AB05 — Desogestrel and ethinylestradiolG03FB10 — Desogestrel and estrogen

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingOtherBiological Availability1
1, 2CompletedTreatmentOvarian Stimulation1
2CompletedBasic ScienceHemostasis / Oral Contraceptives (OC)1
2CompletedTreatmentHealthy Volunteers1
2Unknown StatusTreatmentWomen With PMS1
2, 3CompletedTreatmentOndine Syndrome1
3Active Not RecruitingTreatmentDysfunctional Uterine Bleeding1
3CompletedPreventionContraception1
3CompletedTreatmentHealthy Volunteers1
3RecruitingTreatmentExercise-related Amenorrhea1
3RecruitingTreatmentInfertility, Female / Polycystic Ovaries Syndrome1
4Active Not RecruitingBasic ScienceBone; Disorder, Development and Growth1
4Active Not RecruitingBasic ScienceOther Disorders of Bone Development and Growth1
4CompletedTreatmentInfertilities1
4TerminatedNot AvailableInfertilities1
4Unknown StatusDiagnosticHaemorrhage1
4Unknown StatusTreatmentMenstrual Problem1
4Unknown StatusTreatmentUterine Leiomyomas1
4WithdrawnTreatmentInfertilities2
Not AvailableCompletedNot AvailableContraception1
Not AvailableCompletedNot AvailableContraceptive Usage / Vaginal Epithelial Disruption1
Not AvailableCompletedNot AvailableControlled Ovaria Stimulation1
Not AvailableCompletedHealth Services ResearchOvarian Follicle1
Not AvailableCompletedTreatmentEndometriosis1
Not AvailableRecruitingNot AvailableFemale Sexual Function1
Not AvailableTerminatedTreatmentIn-Vitro Fertilization / Infertilities1
Not AvailableUnknown StatusTreatmentCongenital Central Hypoventilation Syndrome1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Organon Pharmaceuticals
Dosage forms
FormRouteStrength
Kit
TabletOral
Prices
Unit descriptionCostUnit
Mircette 28 0.15-0.02/0.01 mg (21/5) tablet Disp Pack79.99USD disp
Kariva 28 0.15-0.02/0.01 mg (21/5) tablet Disp Pack62.38USD disp
Cyclessa 28 tablet Disp Pack56.39USD disp
Desogen 28 day tablet1.86USD tablet
Cyclessa 28 day tablet1.82USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)109-110Van den Broek, A.J.; US. Patent 3,927,046; December 16, 1975; assigned to Akzona, Inc.
logP4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00301 mg/mLALOGPS
logP4.3ALOGPS
logP4.42ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)17.99ChemAxon
pKa (Strongest Basic)-1.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity95.73 m3·mol-1ChemAxon
Polarizability37.54 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9941
Blood Brain Barrier+0.9619
Caco-2 permeable+0.774
P-glycoprotein substrateSubstrate0.6665
P-glycoprotein inhibitor IInhibitor0.6013
P-glycoprotein inhibitor IINon-inhibitor0.8924
Renal organic cation transporterNon-inhibitor0.7478
CYP450 2C9 substrateNon-substrate0.8183
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateSubstrate0.6794
CYP450 1A2 substrateNon-inhibitor0.8353
CYP450 2C9 inhibitorNon-inhibitor0.7484
CYP450 2D6 inhibitorNon-inhibitor0.9132
CYP450 2C19 inhibitorInhibitor0.8537
CYP450 3A4 inhibitorNon-inhibitor0.764
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6204
Ames testNon AMES toxic0.923
CarcinogenicityNon-carcinogens0.9213
BiodegradationNot ready biodegradable0.9935
Rat acute toxicity2.3315 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7135
hERG inhibition (predictor II)Non-inhibitor0.7626
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as estrane steroids. These are steroids with a structure based on the estrane skeleton.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Estrane steroids
Direct Parent
Estrane steroids
Alternative Parents
17-hydroxysteroids / Delta-4-steroids / Ynones / Tertiary alcohols / Cyclic alcohols and derivatives / Acetylides / Hydrocarbon derivatives
Substituents
17-hydroxysteroid / Hydroxysteroid / Estrane-skeleton / Delta-4-steroid / Ynone / Tertiary alcohol / Cyclic alcohol / Acetylide / Organic oxygen compound / Hydrocarbon derivative
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
terminal acetylenic compound, 17beta-hydroxy steroid (CHEBI:4453) / C21 steroids (gluco/mineralocorticoids, progestogens) and derivatives (C07629) / C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives (LMST02030104)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
Gene Name
PGR
Uniprot ID
P06401
Uniprot Name
Progesterone receptor
Molecular Weight
98979.96 Da
References
  1. Bergink EW, van Meel F, Turpijn EW, van der Vies J: Binding of progestagens to receptor proteins in MCF-7 cells. J Steroid Biochem. 1983 Nov;19(5):1563-70. [PubMed:6645495]
  2. Fuhrmann U, Slater EP, Fritzemeier KH: Characterization of the novel progestin gestodene by receptor binding studies and transactivation assays. Contraception. 1995 Jan;51(1):45-52. [PubMed:7750284]
  3. Kloosterboer HJ, Vonk-Noordegraaf CA, Turpijn EW: Selectivity in progesterone and androgen receptor binding of progestagens used in oral contraceptives. Contraception. 1988 Sep;38(3):325-32. [PubMed:3139361]
  4. Macpherson AM, Archer DF, Leslie S, Charnock-Jones DS, Makkink WK, Smith SK: The effect of etonogestrel on VEGF, oestrogen and progesterone receptor immunoreactivity and endothelial cell number in human endometrium. Hum Reprod. 1999 Dec;14(12):3080-7. [PubMed:10601100]
  5. Charnock-Jones DS, Macpherson AM, Archer DF, Leslie S, Makkink WK, Sharkey AM, Smith SK: The effect of progestins on vascular endothelial growth factor, oestrogen receptor and progesterone receptor immunoreactivity and endothelial cell density in human endometrium. Hum Reprod. 2000 Aug;15 Suppl 3:85-95. [PubMed:11041225]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
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
  1. Fuhrmann U, Slater EP, Fritzemeier KH: Characterization of the novel progestin gestodene by receptor binding studies and transactivation assays. Contraception. 1995 Jan;51(1):45-52. [PubMed:7750284]
  2. Rabe T, Bohlmann MK, Rehberger-Schneider S, Prifti S: Induction of estrogen receptor-alpha and -beta activities by synthetic progestins. Gynecol Endocrinol. 2000 Apr;14(2):118-26. [PubMed:10836199]
  3. Juchem M, Pollow K: Binding of oral contraceptive progestogens to serum proteins and cytoplasmic receptor. Am J Obstet Gynecol. 1990 Dec;163(6 Pt 2):2171-83. [PubMed:2175153]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Inhibitor
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. Kuhl H: Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. 2005 Aug;8 Suppl 1:3-63. doi: 10.1080/13697130500148875. [PubMed:16112947]
  2. Kuhl H: Comparative pharmacology of newer progestogens. Drugs. 1996 Feb;51(2):188-215. [PubMed:8808163]
  3. Korhonen T, Tolonen A, Uusitalo J, Lundgren S, Jalonen J, Laine K: The role of CYP2C and CYP3A in the disposition of 3-keto-desogestrel after administration of desogestrel. Br J Clin Pharmacol. 2005 Jul;60(1):69-75. [PubMed:15963096]

Drug created on June 13, 2005 07:24 / Updated on September 13, 2018 15:35