Drospirenone

Identification

Summary

Drospirenone is a progestin used in oral contraceptive pills for the prevention of pregnancy and other conditions.

Brand Names
Angeliq 0.25/0.5 28 Day, Beyaz 28 Day, Gianvi 28-day, Jasmiel 28 Day, Lo-zumandimine 28 Day, Loryna, Nextstellis 28 Day, Nikki 28 Day, Ocella 28 Day, Safyral 28 Day, Slynd, Syeda 28 Day, Tydemy 28 Day, Vestura, Yasmin, Yasmin 28 Day, Yaz 28 Day, Yaz Plus, Zarah, Zumandimine 28 Day
Generic Name
Drospirenone
DrugBank Accession Number
DB01395
Background

Drospirenone is a synthetic progestin commonly found in the popular oral contraceptive, Yaz in combination with Ethinyl estradiol.19 Most recently, it was approved by both Health Canada and the FDA in combination with Estetrol as an oral contraceptive therapy.27,28 Aside from its contraceptive effects, drospirenone is used with estrogens to control acne and premenstrual dysphoric disorder (PMDD).

Drospirenone has been the subject of widespread safety concern due to the possibility of an increased risk of venous thromboembolism associated with its use.4,7 In 2012, however, a safety statement by the FDA concluded that the increase in the risk of thromboembolism resulting from the use of drospirenone remains unclear, as studies regarding this risk are conflicting. Some studies have demonstrated a significantly increased risk and some demonstrating no risk of thromboembolic events. In its statement, the FDA has mentioned that increased risk of venous thromboembolism with oral contraceptives such as drospirenone exists but remains lower than the risk of this condition during pregnancy and during the postpartum period, and this should be considered when assessing potential risks of hormonal contraceptive use.21

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 366.4932
Monoisotopic: 366.219494826
Chemical Formula
C24H30O3
Synonyms
  • 1,2-Dihydrospirorenone
  • 6β,7β;15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone
  • Dehydrospirorenone
  • Drospirenona
  • Drospirenone
  • Drospirénone
  • Drospirenonum
  • DRSP
External IDs
  • ZK 30595
  • ZK-30595

Pharmacology

Indication

Drospirenone, in combination with ethinyl estradiol or estetrol, is indicated as an oral contraceptive for the prevention of pregnancy.19,28 In addition to its use for contraceptive effects, this combination is used to treat moderate acne vulgaris and the symptoms of premenstrual dysphoric disorder.19,20 The drug has approved indications for combination with estrogens for the treatment of menopause-associated symptoms, such as vasomotor symptoms and vulvovaginal atrophy. Drospirenone combined with estrogen may also may aid in the prevention of osteoporosis in women who have been post-menopausal for at least a year and are not candidates for other therapies.23,25 It can sometimes be found in preparations containing estrogen and folic acid for folic acid replenishment during oral contraception.26

When used for the treatment of acne vulgaris, drospirenone-containing contraceptives should only be used in women ≥14 years of age who have experienced menarche, desire oral contraception, and do not have any contraindications to oral contraceptives.20 Off-label uses for this drug include the treatment of menstrual irregularities, dysmenorrhea, hirsutism, and endometriosis.1,11

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to manageAtrophy of vulvaCombination Product in combination with: Estradiol (DB00783)•••••••••••••••••••• •• •••••• ••••••••••••••
Used in combination to manageModerate to severe vasomotor symptomsCombination Product in combination with: Estradiol (DB00783)••••••••••••••••••
Used in combination to preventNeural tube defects (ntds)Combination Product in combination with: Ethinylestradiol (DB00977), Levomefolic acid (DB11256)•••••••••••••••••••• ••••••••• ••••••
Used in combination to managePremenstrual dysphoric disorder (pmdd)Combination Product in combination with: Ethinylestradiol (DB00977), Levomefolic acid (DB11256)•••••••••••••••• ••••••
Used in combination to manageVulvo vaginal atrophyCombination Product in combination with: Estradiol (DB00783)•••••••••••••••••••• •• •••••• ••••••••••••••
Associated Therapies
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Pharmacodynamics

Drospirenone inhibits the maturation of follicles and inhibits ovulation, preventing pregnancy. It has antiandrogen effects, improving acne and hirsutism. When combined with ethinyl estradiol, it has been shown to have favorable effects on the plasma lipid profile.20 Due to its similarity to naturally occurring progesterone, drospirenone is thought to be associated with a lower incidence of progesterone contraceptive related adverse effects, such as breast tenderness and mood swings.1

A note on venous thromboembolism risk and antimineralcorticoid effects

As with other oral contraceptives, the risk of venous thromboembolism and cardiovascular events may be increased when drospirenone is taken. The risk is especially higher in smokers and women aged 35 and older. Women taking this drug should be advised not to smoke. In addition, drospirenone, due to its antimineralcorticoid effects, may increase the risk of hyperkalemia. Patients at high risk for hyperkalemia should not be administered this drug. Consult the official prescribing information for detailed and updated information on the cardiovascular and other risks associated with drospirenone use.19,20,23

Mechanism of action

Drospirenone and ethinyl estradiol in combination suppress the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH), preventing ovulation. Other changes induced by this drug which may aid in the prevention of pregnancy include alterations in cervical mucus consistency, hindering sperm movement, and lowering the chance of embryo implantation.20

Drospirenone is an analog of the diuretic spironolactone, which exerts anti-mineralocorticoid activity, blocking aldosterone receptors, which increases sodium and water excretion.1 Studies in animals have demonstrated that drospirenone administration leads to antiandrogenic activity. This activity helps to oppose the effects of naturally occurring androgens, inhibiting the binding of dihydrotestosterone (DHT) to its receptor, and preventing androgen synthesis in the ovaries, helping to treat acne and hirsutism.1,12,19 Drospirenone may also decrease the level of edema in sebaceous follicle during the second half of the menstrual cycle, when acne often appears.19

TargetActionsOrganism
AMineralocorticoid receptor
antagonist
Humans
AAndrogen receptor
antagonist
Humans
AProgesterone receptor
agonist
Humans
UGlucocorticoid receptor
binder
Humans
Absorption

The absolute bioavailability of drospirenone is approximately 76% due to first-pass effects.13,19 The maximum plasma concentration of drospirenone occurs within 1 to 2 hours after oral administration and is estimated to range between 60 and 87 ng/mL.1 A European prescribing monograph for the combination product of estradiol and drospirenone indicates that drospirenone is both completely and rapidly absorbed. It reports a Cmax of 21.9 ng/ml, achieved approximately 1-hour post-administration. The absolute bioavailability is reported to range between 76 to 85%.23

Volume of distribution

The volume of distribution of drospirenone is estimated to be 4 L/kg, according to the FDA label for Yaz.19 Prescribing information from a combination of estradiol and drospirenone estimates the volume of distribution to range from 3.7- 4.2 L/kg.23

Protein binding

Drospirenone is about 95% to 97% bound to serum plasma protein, likely to albumin.1 During in vitro studies, drospirenone was found to bind with low affinity to sex hormone-binding globulin (SHBG).20 Another reference indicates that drospirenone binds to serum albumin but does not bind to sex hormone-binding globulin (SHBG), nor corticoid binding globulin (CBG). Only 3-5% of the total drospirenone concentration is measured as a free steroid. 23

Metabolism

Drospirenone is heavily metabolized. The two major inactive metabolites identified are the acid form of drospirenone produced by the opening of its lactone ring, known as M11, and the 4,5-dihydro-drospirenone-3-sulfate (M14).1,13 Drospirenone also undergoes oxidative metabolism via the hepatic cytochrome enzyme CYP3A4.17,18,23

Hover over products below to view reaction partners

Route of elimination

Various metabolites of drospirenone are measured in the urine and feces. Drospirenone elimination from the body is almost after 10 days post-administration1 when negligible amounts of drospirenone are found unchanged in both the urine and feces.23 Between 38% to 47% of the metabolites are identified as glucuronide and sulfate conjugates in the urine. In the feces, approximately 17% to 20% of identifiable metabolites are found to be excreted as glucuronides and sulfates.1

Half-life

The serum half-life of drospirenone is estimated to be 30 hours.13 The half-life of drospirenone metabolite excretion in the urine and feces is approximately 40 hours.23

Clearance

Drospirenone is rapidly cleared, typically within 2-3 days of administration of the last active tablet.14 The rate of clearance of drospirenone calculated in the serum ranges from 1.2-1.5 ml/min/kg, however, this value can vary by up to 25% according to the patient.23

Adverse Effects
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Toxicity

The oral LD50 of drospirenone in rats is >2000 mg/kg.22

Overdose information An overdose of drospirenone, like other oral contraceptives, may lead to cause nausea or withdrawal bleeding. For drospirenone in particular, as an analog of spironolactone, may affect the levels of serum sodium and potassium. Their concentrations should be monitored in cases of overdose in addition to monitoring from metabolic acidosis and hyperkalemia, which may also result.15,19

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirDrospirenone may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
AbametapirThe serum concentration of Drospirenone can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Drospirenone can be increased when combined with Abatacept.
AbciximabThe risk or severity of adverse effects can be increased when Drospirenone is combined with Abciximab.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Drospirenone.
Food Interactions
  • Avoid St. John's Wort.
  • Take at the same time every day.
  • Take with or without food.

Products

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Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SlyndTablet4 mgOralDuchesnay Inc.2022-04-20Not applicableCanada flag
SlyndKit; Tablet, film coated4 mg/1OralExeltis Usa, Inc.2019-06-06Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Aliane 0,02 mg/3 mg FilmtablettenDrospirenone (3 mg) + Ethinylestradiol (0.02 mg)Tablet, film coatedOralBayer Austria Ges.M.B.H.2006-05-26Not applicableAustria flag
AngeliqDrospirenone (0.25 mg/1) + Estradiol (0.5 mg/1)Tablet, film coatedOralBayer HealthCare Pharmaceuticals Inc.2012-02-29Not applicableUS flag
ANGELIQDrospirenone (2 mg) + Estradiol (1 mg)Tablet, film coatedOralBayer Indonesia2018-03-092027-09-01Indonesia flag
AngeliqDrospirenone (0.5 mg/1) + Estradiol (1 mg/1)Tablet, film coatedOralBayer HealthCare Pharmaceuticals Inc.2005-11-28Not applicableUS flag
ANGELIQDrospirenone (2 mg) + Estradiol hemihydrate (1 mg)Tablet, film coatedOral2017-01-01Not applicableGermany flag

Categories

ATC Codes
G03AA18 — Drospirenone and estetrolG03AC10 — DrospirenoneG03FA17 — Drospirenone and estrogenG03AA12 — Drospirenone and ethinylestradiol
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as spironolactones and derivatives. These are steroid lactones with a structure based on the spironolactone skeleton.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Steroid lactones
Direct Parent
Spironolactones and derivatives
Alternative Parents
Cyclohexenones / Gamma butyrolactones / Tetrahydrofurans / Carboxylic acid esters / Oxacyclic compounds / Monocarboxylic acids and derivatives / Organic oxides / Hydrocarbon derivatives
Substituents
Aliphatic heteropolycyclic compound / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Cyclic ketone / Cyclohexenone / Gamma butyrolactone / Hydrocarbon derivative / Ketone / Lactone
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
3-oxo steroid, 3-oxo Delta(4)-steroid, steroid lactone (CHEBI:50838)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
N295J34A25
CAS number
67392-87-4
InChI Key
METQSPRSQINEEU-HXCATZOESA-N
InChI
InChI=1S/C24H30O3/c1-22-6-3-12(25)9-17(22)13-10-14(13)20-16(22)4-7-23(2)21(20)15-11-18(15)24(23)8-5-19(26)27-24/h9,13-16,18,20-21H,3-8,10-11H2,1-2H3/t13-,14+,15-,16+,18+,20-,21+,22-,23+,24+/m1/s1
IUPAC Name
(1R,2R,4R,10R,11S,14S,15S,16S,18S,19S)-10,14-dimethylspiro[hexacyclo[9.8.0.0^{2,4}.0^{5,10}.0^{14,19}.0^{16,18}]nonadecane-15,2'-oxolan]-5-ene-5',7-dione
SMILES
[H][C@@]12C[C@]1([H])[C@@]1([H])[C@]3([H])[C@]4([H])C[C@]4([H])[C@@]4(CCC(=O)O4)[C@@]3(C)CC[C@]1([H])[C@@]1(C)CCC(=O)C=C21

References

Synthesis Reference

DOI: 10.1002/cjoc.201201147

General References
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. [Article]
  2. Wichianpitaya J, Taneepanichskul S: A comparative efficacy of low-dose combined oral contraceptives containing desogestrel and drospirenone in premenstrual symptoms. Obstet Gynecol Int. 2013;2013:487143. doi: 10.1155/2013/487143. Epub 2013 Feb 20. [Article]
  3. Larivee N, Suissa S, Khosrow-Khavar F, Tagalakis V, Filion KB: Drospirenone-containing oral contraceptive pills and the risk of venous thromboembolism: a systematic review of observational studies. BJOG. 2017 Sep;124(10):1490-1499. doi: 10.1111/1471-0528.14623. Epub 2017 May 5. [Article]
  4. Oedingen C, Scholz S, Razum O: Systematic review and meta-analysis of the association of combined oral contraceptives on the risk of venous thromboembolism: The role of the progestogen type and estrogen dose. Thromb Res. 2018 May;165:68-78. doi: 10.1016/j.thromres.2018.03.005. Epub 2018 Mar 15. [Article]
  5. Li J, Ren J, Sun W: A comparative systematic review of Yasmin (drospirenone pill) versus standard treatment options for symptoms of polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2017 Mar;210:13-21. doi: 10.1016/j.ejogrb.2016.11.013. Epub 2016 Nov 16. [Article]
  6. Lopez LM, Kaptein AA, Helmerhorst FM: Oral contraceptives containing drospirenone for premenstrual syndrome. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD006586. doi: 10.1002/14651858.CD006586.pub4. [Article]
  7. Authors unspecified: ACOG Committee Opinion Number 540: Risk of venous thromboembolism among users of drospirenone-containing oral contraceptive pills. Obstet Gynecol. 2012 Nov;120(5):1239-42. doi: http://10.1097/AOG.0b013e318277c93b. [Article]
  8. Kluft C, Zimmerman Y, Mawet M, Klipping C, Duijkers IJ, Neuteboom J, Foidart JM, Bennink HC: Reduced hemostatic effects with drospirenone-based oral contraceptives containing estetrol vs. ethinyl estradiol. Contraception. 2017 Feb;95(2):140-147. doi: 10.1016/j.contraception.2016.08.018. Epub 2016 Sep 1. [Article]
  9. Regidor PA, Schindler AE: Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestogens: dienogest and drospirenone. Oncotarget. 2017 Aug 3;8(47):83334-83342. doi: 10.18632/oncotarget.19833. eCollection 2017 Oct 10. [Article]
  10. Momoeda M, Kondo M, Elliesen J, Yasuda M, Yamamoto S, Harada T: Efficacy and safety of a flexible extended regimen of ethinylestradiol/drospirenone for the treatment of dysmenorrhea: a multicenter, randomized, open-label, active-controlled study. Int J Womens Health. 2017 May 2;9:295-305. doi: 10.2147/IJWH.S134576. eCollection 2017. [Article]
  11. Suvarna Y, Maity N, Kalra P, Shivamurthy MC: Comparison of efficacy of metformin and oral contraceptive combination of ethinyl estradiol and drospirenone in polycystic ovary syndrome. J Turk Ger Gynecol Assoc. 2016 Jan 12;17(1):6-9. doi: 10.5152/jtgga.2016.16129. eCollection 2016. [Article]
  12. Mathur R, Levin O, Azziz R: Use of ethinylestradiol/drospirenone combination in patients with the polycystic ovary syndrome. Ther Clin Risk Manag. 2008 Apr;4(2):487-92. doi: 10.2147/tcrm.s6864. [Article]
  13. Rapkin AJ, Winer SA: Drospirenone: a novel progestin. Expert Opin Pharmacother. 2007 May;8(7):989-99. doi: 10.1517/14656566.8.7.989 . [Article]
  14. Breech LL, Braverman PK: Safety, efficacy, actions, and patient acceptability of drospirenone/ethinyl estradiol contraceptive pills in the treatment of premenstrual dysphoric disorder. Int J Womens Health. 2010 Aug 9;1:85-95. [Article]
  15. Bird ST, Pepe SR, Etminan M, Liu X, Brophy JM, Delaney JA: The association between drospirenone and hyperkalemia: a comparative-safety study. BMC Clin Pharmacol. 2011 Dec 30;11:23. doi: 10.1186/1472-6904-11-23. [Article]
  16. Zhang N, Shon J, Kim MJ, Yu C, Zhang L, Huang SM, Lee L, Tran D, Li L: Role of CYP3A in Oral Contraceptives Clearance. Clin Transl Sci. 2018 May;11(3):251-260. doi: 10.1111/cts.12499. Epub 2017 Oct 6. [Article]
  17. Cadeddu G, Deidda A, Stochino ME, Velluti N, Burrai C, Del Zompo M: Clozapine toxicity due to a multiple drug interaction: a case report. J Med Case Rep. 2015 Apr 2;9:77. doi: 10.1186/s13256-015-0547-2. [Article]
  18. Wiesinger H, Berse M, Klein S, Gschwend S, Hochel J, Zollmann FS, Schutt B: Pharmacokinetic interaction between the CYP3A4 inhibitor ketoconazole and the hormone drospirenone in combination with ethinylestradiol or estradiol. Br J Clin Pharmacol. 2015 Dec;80(6):1399-410. doi: 10.1111/bcp.12745. Epub 2015 Oct 28. [Article]
  19. YAZ fda label [Link]
  20. Yaz Bayer monograph [Link]
  21. 2012 FDA safety statement, YAZ [Link]
  22. FDA pharmacology review, Drospirenone [Link]
  23. Angeliq EU label [Link]
  24. drospirenone/ethinyl estradiol - Drug Summary [Link]
  25. Angeliq FDA label [Link]
  26. Safyral FDA label [Link]
  27. Product monograph: Nexstellis (estetrol and drospirenone) oral tablets [Link]
  28. FDA Approved Drug Products: NEXTSTELLIS (drospirenone and estetrol) tablets for oral use [Link]
  29. FDA Approved Drug Products: YASMIN (drospirenone/ethinyl estradiol) tablets, for oral use [Link]
Human Metabolome Database
HMDB0015467
KEGG Drug
D03917
PubChem Compound
68873
PubChem Substance
46507653
ChemSpider
62105
BindingDB
150275
RxNav
11636
ChEBI
50838
ChEMBL
CHEMBL1509
ZINC
ZINC000003927200
Therapeutic Targets Database
DAP001206
PharmGKB
PA164749409
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Drospirenone
FDA label
Download (292 KB)
MSDS
Download (567 KB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableContraception5somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailablePolycystic Ovarian Syndrome (PCOS) / Syndrome, Metabolic1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailablePostmenopausal / Postmenopausal Osteoporosis1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentDepression / Premenstrual Syndrome (PMS)1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentEstro-progestin Drugs / Polycystic Ovarian Syndrome (PCOS)1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, film coatedOral
Kit; tablet, film coatedOral
Tablet, film coatedOral0.03 MG
Tablet, coatedOral4 mg
SolutionOral
TabletOral3.000 mg
Kit; tabletOral
Tablet, film coatedOral
Tablet, film coatedOral4 MG
Kit; tablet, film coatedOral4 mg/1
TabletOral4 mg
Capsule, liquid filledOral
TabletOral
Tablet, coatedOral
Tablet, film coatedOral3 mg
KitOral
Tablet, film coatedOral0.02 MG
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6787531No2004-09-072020-08-31US flag
US6933395No2005-08-232017-08-11US flag
US8906890No2014-12-092031-10-22US flag
US6987101No2006-01-172017-12-22US flag
US7163931No2007-01-162021-12-20US flag
US6958326No2005-10-252021-12-20US flag
US5798338No1998-08-252015-07-10US flag
US6441168No2002-08-272022-07-30US flag
US8617597No2013-12-312030-02-08US flag
US10179140No2019-01-152031-06-28US flag
US9603860No2017-03-282031-06-28US flag
US10603281No2020-03-312031-06-08US flag
US10849857No2020-12-012031-06-28US flag
US7732430No2010-06-082025-03-02US flag
US10987364No2021-04-272031-06-28US flag
US11123299No2021-09-212031-06-28US flag
US11291633No2011-06-282031-06-28US flag
US11291632No2011-06-282031-06-28US flag
US11351122No2011-06-282031-06-28US flag
US11413249No2011-06-282031-06-28US flag
US11439598No2011-06-282031-06-28US flag
US11478487No2011-06-282031-06-28US flag
US11504334No2011-06-282031-06-28US flag
US11617751No2010-07-172030-07-17US flag
US11793760No2016-06-172036-06-17US flag
US11951213No2011-06-282031-06-28US flag
US11957694No2016-06-172036-06-17US flag
US11964055No2016-06-172036-06-17US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)196-200https://www.chemicalbook.com/ChemicalProductProperty_US_CB8695608.aspx
boiling point (°C)552.2https://www.lookchem.com/Drospirenone/
logP3.08https://pdf.hres.ca/dpd_pm/00042999.PDF
logS-5.2http://www.hmdb.ca/metabolites/HMDB0015467
pKa-5http://www.hmdb.ca/metabolites/HMDB0015467
Predicted Properties
PropertyValueSource
Water Solubility0.00225 mg/mLALOGPS
logP2.36ALOGPS
logP3.37Chemaxon
logS-5.2ALOGPS
pKa (Strongest Acidic)18.52Chemaxon
pKa (Strongest Basic)-5Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area43.37 Å2Chemaxon
Rotatable Bond Count0Chemaxon
Refractivity101.68 m3·mol-1Chemaxon
Polarizability41.81 Å3Chemaxon
Number of Rings7Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9383
Caco-2 permeable+0.6376
P-glycoprotein substrateSubstrate0.6524
P-glycoprotein inhibitor IInhibitor0.6171
P-glycoprotein inhibitor IINon-inhibitor0.6726
Renal organic cation transporterNon-inhibitor0.7005
CYP450 2C9 substrateNon-substrate0.796
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6964
CYP450 1A2 substrateNon-inhibitor0.5534
CYP450 2C9 inhibitorNon-inhibitor0.8665
CYP450 2D6 inhibitorNon-inhibitor0.9336
CYP450 2C19 inhibitorNon-inhibitor0.7754
CYP450 3A4 inhibitorNon-inhibitor0.8355
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8541
Ames testNon AMES toxic0.9163
CarcinogenicityNon-carcinogens0.9505
BiodegradationNot ready biodegradable0.9757
Rat acute toxicity1.9430 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9393
hERG inhibition (predictor II)Non-inhibitor0.8215
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (37.1 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0w9c-0169000000-37155c35a2dfebdf3836
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0009000000-d2c2b3f0083127b93331
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-014j-0009000000-fec0b9559b578e9c9431
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0009000000-e83f0561c8b894209b60
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014j-0209000000-16e3f1168fe085039712
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00xu-1019000000-7ac789c15184524f4e22
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-066r-0629000000-80294d71e68e61c9f972
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-198.3961196
predicted
DarkChem Lite v0.1.0
[M-H]-198.4750196
predicted
DarkChem Lite v0.1.0
[M-H]-197.7604196
predicted
DarkChem Lite v0.1.0
[M-H]-188.11028
predicted
DeepCCS 1.0 (2019)
[M+H]+198.9765196
predicted
DarkChem Lite v0.1.0
[M+H]+199.0630196
predicted
DarkChem Lite v0.1.0
[M+H]+197.9431196
predicted
DarkChem Lite v0.1.0
[M+H]+189.834
predicted
DeepCCS 1.0 (2019)
[M+Na]+199.4102196
predicted
DarkChem Lite v0.1.0
[M+Na]+198.7850196
predicted
DarkChem Lite v0.1.0
[M+Na]+196.16295
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels
Specific Function
DNA-binding transcription factor activity
Gene Name
NR3C2
Uniprot ID
P08235
Uniprot Name
Mineralocorticoid receptor
Molecular Weight
107080.615 Da
References
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. [Article]
  2. Fuhrmann U, Krattenmacher R, Slater EP, Fritzemeier KH: The novel progestin drospirenone and its natural counterpart progesterone: biochemical profile and antiandrogenic potential. Contraception. 1996 Oct;54(4):243-51. [Article]
  3. Muhn P, Fuhrmann U, Fritzemeier KH, Krattenmacher R, Schillinger E: Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Ann N Y Acad Sci. 1995 Jun 12;761:311-35. doi: 10.1111/j.1749-6632.1995.tb31386.x. [Article]
  4. Oelkers WK: Effects of estrogens and progestogens on the renin-aldosterone system and blood pressure. Steroids. 1996 Apr;61(4):166-71. [Article]
  5. Oelkers W: Antimineralocorticoid activity of a novel oral contraceptive containing drospirenone, a unique progestogen resembling natural progesterone. Eur J Contracept Reprod Health Care. 2002 Dec;7 Suppl 3:19-26; discussion 42-3. [Article]
  6. Oelkers W: Drospirenone, a progestogen with antimineralocorticoid properties: a short review. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):255-61. doi: 10.1016/j.mce.2003.10.030. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
Curator comments
References indicate a lower affinity to the androgen receptor.
General Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849). Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3
Specific Function
androgen binding
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
99187.115 Da
References
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. [Article]
  2. Muhn P, Fuhrmann U, Fritzemeier KH, Krattenmacher R, Schillinger E: Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Ann N Y Acad Sci. 1995 Jun 12;761:311-35. doi: 10.1111/j.1749-6632.1995.tb31386.x. [Article]
  3. Oelkers W: Drospirenone, a progestogen with antimineralocorticoid properties: a short review. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):255-61. doi: 10.1016/j.mce.2003.10.030. [Article]
  4. Yaz Bayer monograph [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General 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. Depending on the isoform, progesterone receptor functions as a transcriptional activator or repressor
Specific Function
ATPase binding
Gene Name
PGR
Uniprot ID
P06401
Uniprot Name
Progesterone receptor
Molecular Weight
98979.96 Da
References
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. [Article]
  2. Bray JD, Jelinsky S, Ghatge R, Bray JA, Tunkey C, Saraf K, Jacobsen BM, Richer JK, Brown EL, Winneker RC, Horwitz KB, Lyttle CR: Quantitative analysis of gene regulation by seven clinically relevant progestins suggests a highly similar mechanism of action through progesterone receptors in T47D breast cancer cells. J Steroid Biochem Mol Biol. 2005 Dec;97(4):328-41. Epub 2005 Sep 12. [Article]
  3. Fuhrmann U, Krattenmacher R, Slater EP, Fritzemeier KH: The novel progestin drospirenone and its natural counterpart progesterone: biochemical profile and antiandrogenic potential. Contraception. 1996 Oct;54(4):243-51. [Article]
  4. Arias-Loza PA, Hu K, Schafer A, Bauersachs J, Quaschning T, Galle J, Jazbutyte V, Neyses L, Ertl G, Fritzemeier KH, Hegele-Hartung C, Pelzer T: Medroxyprogesterone acetate but not drospirenone ablates the protective function of 17 beta-estradiol in aldosterone salt-treated rats. Hypertension. 2006 Nov;48(5):994-1001. Epub 2006 Sep 25. [Article]
  5. Sitruk-Ware R: New progestagens for contraceptive use. Hum Reprod Update. 2006 Mar-Apr;12(2):169-78. Epub 2005 Nov 16. [Article]
  6. Sitruk-Ware R: New progestogens: a review of their effects in perimenopausal and postmenopausal women. Drugs Aging. 2004;21(13):865-83. [Article]
  7. Muhn P, Fuhrmann U, Fritzemeier KH, Krattenmacher R, Schillinger E: Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Ann N Y Acad Sci. 1995 Jun 12;761:311-35. doi: 10.1111/j.1749-6632.1995.tb31386.x. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
Curator comments
References indicate a weak binding affinity to the glucocorticoid receptor.
General Function
Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity)
Specific Function
core promoter sequence-specific DNA binding
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
References
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. [Article]
  2. Muhn P, Fuhrmann U, Fritzemeier KH, Krattenmacher R, Schillinger E: Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Ann N Y Acad Sci. 1995 Jun 12;761:311-35. doi: 10.1111/j.1749-6632.1995.tb31386.x. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
Curator comments
Amenorrheic patients on drospirenone were found to exhibit inhibition of COX-2 expression. Those with breakthrough bleeding on drospirenone were found to have increased COX-2 expression.
General Function
Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response (PubMed:11939906, PubMed:16373578, PubMed:19540099, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins (PubMed:11939906, PubMed:19540099). In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids (PubMed:27642067). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (PubMed:22942274). Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols (PubMed:11034610, PubMed:11192938, PubMed:9048568, PubMed:9261177). Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation (PubMed:12391014). Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) (PubMed:12391014). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 (PubMed:21206090). In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection (PubMed:26236990). In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (PubMed:22068350, PubMed:26282205). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity)
Specific Function
enzyme binding
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Maia H Jr, Casoy J, Athayde C, Valente Filho J, Coutinho EM: The effect of a continuous regimen of drospirenone 3 mg/ethinylestradiol 30 microg on Cox-2 and Ki-67 expression in the endometrium. Eur J Contracept Reprod Health Care. 2010 Feb;15(1):35-40. doi: 10.3109/13625180903383928. [Article]
  2. Maia H Jr, Haddad C, Pinheiro N, Casoy J: The effect of oral contraceptives on aromatase and Cox-2 expression in the endometrium of patients with idiopathic menorrhagia or adenomyosis. Int J Womens Health. 2013 Jun 13;5:293-9. doi: 10.2147/IJWH.S45093. Print 2013. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
This enzyme activity is based on the results of an in vivo study with rat and dog subjects.
General Function
Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic acid esters. Mediates an enzymatic protection of low density lipoproteins against oxidative modification and the consequent series of events leading to atheroma formation
Specific Function
acyl-L-homoserine-lactone lactonohydrolase activity
Gene Name
PON1
Uniprot ID
P27169
Uniprot Name
Serum paraoxonase/arylesterase 1
Molecular Weight
39730.99 Da
References
  1. Koitka M, Hochel J, Gieschen H, Borchert HH: Improving the ex vivo stability of drug ester compounds in rat and dog serum: inhibition of the specific esterases and implications on their identity. J Pharm Biomed Anal. 2010 Feb 5;51(3):664-78. doi: 10.1016/j.jpba.2009.09.023. Epub 2009 Sep 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function
1,8-cineole 2-exo-monooxygenase activity
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Wiesinger H, Berse M, Klein S, Gschwend S, Hochel J, Zollmann FS, Schutt B: Pharmacokinetic interaction between the CYP3A4 inhibitor ketoconazole and the hormone drospirenone in combination with ethinylestradiol or estradiol. Br J Clin Pharmacol. 2015 Dec;80(6):1399-410. doi: 10.1111/bcp.12745. Epub 2015 Oct 28. [Article]
  2. Cadeddu G, Deidda A, Stochino ME, Velluti N, Burrai C, Del Zompo M: Clozapine toxicity due to a multiple drug interaction: a case report. J Med Case Rep. 2015 Apr 2;9:77. doi: 10.1186/s13256-015-0547-2. [Article]
  3. Zhang N, Shon J, Kim MJ, Yu C, Zhang L, Huang SM, Lee L, Tran D, Li L: Role of CYP3A in Oral Contraceptives Clearance. Clin Transl Sci. 2018 May;11(3):251-260. doi: 10.1111/cts.12499. Epub 2017 Oct 6. [Article]
  4. Angeliq EU label [Link]

Drug created at July 08, 2007 17:03 / Updated at May 31, 2023 07:29