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Identification
NameDrospirenone
Accession NumberDB01395
TypeSmall Molecule
GroupsApproved
Description

Drospirenone is a synthetic progestin that is an analog to spironolactone. It is found in a number of birth control formulations. Drospirenone differs from other synthetic progestins in that its pharmacological profile in preclinical studies shows it to be closer to the natural progesterone. As such it has anti-mineralocorticoid properties, counteracts the estrogen-stimulated activity of the renin-angiotensin-aldosterone system, and is not androgenic. It was shown in animal studies that drospirenone exhibits antiandrogenic activity judging from accessory sex gland growth in castrated, androgen-treated, juvenile rats.

Structure
Thumb
Synonyms
SynonymLanguageCode
1,2-DihydrospirorenoneNot AvailableNot Available
6beta,7Beta;15beta,16beta-dimethylene-3-oxo-17alpha-pregn-4-ene-21,17-carbolactoneNot AvailableNot Available
6β,7β,15β,16β-dimethylene-3-oxo-17α-pregn-4-ene-21,17 carbolactoneNot AvailableNot Available
DehydrospirorenoneNot AvailableNot Available
DrospirenonaSpanishINN
DrospirenonumLatinINN
DRSPNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
SafyralBayer HealthCare Pharmaceuticals Inc.
YasminBayer HealthCare Pharmaceuticals Inc.
Yaz Bayer HealthCare Pharmaceuticals Inc.
Brand mixtures
Brand NameIngredients
Safyraldrospirenone + ethinyl estradiol + levomefolate calcium + levomefolate calcium
Yasmindrospirenone + ethinylestradiol
Yazdrospirenone + ethinylestradiol
Categories
CAS number67392-87-4
WeightAverage: 366.4932
Monoisotopic: 366.219494826
Chemical FormulaC24H30O3
InChI KeyMETQSPRSQINEEU-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
Mass Specshow(37.1 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassSteroid Lactones
Direct parentSteroid Lactones
Alternative parentsEstrogens and Derivatives; Other Steroids and Derivatives; Tetrahydrofurans; Oxolanes; Ketones; Lactones; Carboxylic Acid Esters; Polyamines
Substituentsestrane-skeleton; other-steroid-skeleton; gamma butyrolactone; oxolane; tetrahydrofuran; lactone; ketone; carboxylic acid ester; polyamine; carboxylic acid derivative; carbonyl group
Classification descriptionThis compound belongs to the steroid lactones. These are sterol lipids containing a lactone moiety linked to the steroid skeleton.
Pharmacology
IndicationFor the prevention of pregnancy in women who elect an oral contraceptive.
PharmacodynamicsDrospirenone differs from other synthetic progestins in that its pharmacological profile in preclinical studies shows it to be closer to the natural progesterone. As such it has anti-mineralocorticoid properties, counteracts the estrogen-stimulated activity of the renin-angiotensin-aldosterone system, and is not androgenic.
Mechanism of actionProgestins such as drospirenone diffuse freely into target cells in the female reproductive tract, mammary gland, hypothalamus, and the pituitary and bind to the progesterone receptor. Once bound to the receptor, progestins slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH surge.
AbsorptionOral bioavailability is approximately 76%.
Volume of distributionNot Available
Protein binding95-97%
Metabolism

Extensively metabolized following oral or intravenous administration. The two major metabolites are inactive and are formed independent of the CYP450 enzyme system. The metabolites are the acid form of drospirenone formed by opening of the lactone ring and the 4,5-dihydro-drospirenone-3-sulfate.

SubstrateEnzymesProduct
Drospirenone
Not Available
4,5-dihydro-drospirenone-3-sulfateDetails
Route of eliminationNot Available
Half life30 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9383
Caco-2 permeable + 0.6376
P-glycoprotein substrate Substrate 0.6524
P-glycoprotein inhibitor I Inhibitor 0.6171
P-glycoprotein inhibitor II Non-inhibitor 0.6726
Renal organic cation transporter Non-inhibitor 0.7005
CYP450 2C9 substrate Non-substrate 0.796
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.6964
CYP450 1A2 substrate Non-inhibitor 0.5534
CYP450 2C9 substrate Non-inhibitor 0.8665
CYP450 2D6 substrate Non-inhibitor 0.9336
CYP450 2C19 substrate Non-inhibitor 0.7754
CYP450 3A4 substrate Non-inhibitor 0.8355
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8541
Ames test Non AMES toxic 0.9163
Carcinogenicity Non-carcinogens 0.9505
Biodegradation Not ready biodegradable 0.9757
Rat acute toxicity 1.9430 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9393
hERG inhibition (predictor II) Non-inhibitor 0.8215
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral0.451 mg levomefolate calcium
TabletOral3 mg drospirenone (DRSP), 0.03 mg ethinyl estradiol (EE) as betadex clathrate and 0.451 mg levomefol
PricesNot Available
Patents
CountryPatent NumberApprovedExpires (estimated)
United States69333952001-05-112017-08-11
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00225ALOGPS
logP2.36ALOGPS
logP3.37ChemAxon
logS-5.2ALOGPS
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
Spectra
SpectraNot Available
References
Synthesis Reference

DOI: 10.1002/cjoc.201201147

General Reference
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. Pubmed
  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. Pubmed
External Links
ResourceLink
KEGG DrugD03917
PubChem Compound68873
PubChem Substance46507653
ChemSpider62105
ChEBI50838
ChEMBLCHEMBL1509
Therapeutic Targets DatabaseDAP001206
PharmGKBPA164749409
Drug Product Database2261731
RxListhttp://www.rxlist.com/yaz-drug.htm
Drugs.comhttp://www.drugs.com/yaz.html
WikipediaDrospirenone
ATC CodesNot Available
AHFS Codes
  • 68:12
PDB EntriesNot Available
FDA labelshow(292 KB)
MSDSshow(567 KB)
Interactions
Drug Interactions
Drug
ArtemetherArtemether may decrease the effectiveness of drospirinone by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
BenazeprilIncreased risk of hyperkalemia
BexaroteneBexarotene may decrease the serum concentration of Contraceptives (Progestins). Since bexarotene is teratogenic and can lower serum concentrations of drospirenone, it is advised that women of childbearing potential use two forms of contraception (including at least one non-hormonal form).
BoceprevirBoceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
CandesartanIncreased risk of hyperkalemia
CaptoprilIncreased risk of hyperkalemia
CilazaprilIncreased risk of hyperkalemia
ColesevelamBile Acid Sequestrants may decrease the serum concentration of Contraceptives (Progestins). Administer oral progestin-containing contraceptives at least 1-4 hours prior to or 4-6 hours after administration of a bile acid sequestrant. Consider alternatives in order to avoid this combination when possible, due to the risk for impaired contraceptive effectiveness.
EnalaprilIncreased risk of hyperkalemia
EprosartanIncreased risk of hyperkalemia
FosinoprilIncreased risk of hyperkalemia
HeparinHeparin can increase risk of hyperkalemia for patients on drospirenone
IrbesartanIncreased risk of hyperkalemia
LisinoprilIncreased risk of hyperkalemia
LosartanIncreased risk of hyperkalemia
OlmesartanIncreased risk of hyperkalemia
PerindoprilIncreased risk of hyperkalemia
PotassiumIncreased risk of hyperkalemia
QuinaprilIncreased risk of hyperkalemia
RamiprilIncreased risk of hyperkalemia
TelmisartanTelmisartan may increase the hyperkalemic effect of Drospirenone. Monitor for increased serum potassium concentrations during concomitant therapy.
ThiopentalThiopental may decrease the effect of Drospirenone. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.
TrandolaprilIncreased risk of hyperkalemia. Monitor serum potassium levels.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
TretinoinOral Tretinoin may decrease the effect of oral contraceptive, Drospirenone. An alternate form of contraception should be used during concomitant therapy.
TriamtereneIncreased risk of hyperkalemia
WarfarinDrospirenone may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if drospirenone is initiated, discontinued or dose changed.
Food Interactions
  • Food reduces the rate of absorption, but not the extent of absorption.

Targets

1. Progesterone receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Progesterone receptor P06401 Details

References:

  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  5. Sitruk-Ware R: New progestagens for contraceptive use. Hum Reprod Update. 2006 Mar-Apr;12(2):169-78. Epub 2005 Nov 16. Pubmed
  6. Sitruk-Ware R: New progestogens: a review of their effects in perimenopausal and postmenopausal women. Drugs Aging. 2004;21(13):865-83. Pubmed

2. Mineralocorticoid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Mineralocorticoid receptor P08235 Details

References:

  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. Pubmed
  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. Pubmed
  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. Pubmed
  4. Oelkers WK: Effects of estrogens and progestogens on the renin-aldosterone system and blood pressure. Steroids. 1996 Apr;61(4):166-71. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Androgen receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Androgen receptor P10275 Details

References:

  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. Pubmed

Enzymes

1. Prostaglandin G/H synthase 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 2 P35354 Details

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. Pubmed

2. Cholinesterase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cholinesterase P06276 Details

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. Epub 2009 Sep 23. Pubmed

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Drug created on July 08, 2007 11:03 / Updated on September 16, 2013 17:14