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targets (3) enzymes (2)
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Identification
Name Drospirenone
Accession Number DB01395
Type small molecule
Groups approved
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.
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Synonyms
6β,7β,15β,16β-dimethylene-3-oxo-17α-pregn-4-ene-21,17 carbolactone
Drospirenona [inn-spanish]
Drospirenonum [inn-latin]
DRSP
Salts Not Available
Brand names Not Available
Brand mixtures
Brand Name Ingredients
Yasmin drospirenone + ethinylestradiol
Yaz drospirenone + ethinylestradiol
Categories
  • Progestins
  • Aldosterone Antagonists
CAS number 67392-87-4
Weight Average: 366.4932
Monoisotopic: 366.219494826
Chemical Formula C24H30O3
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes
  • Steroids and Steroid Derivatives
Substructures
  • Steroids and Steroid Derivatives
  • Carboxylic Acids and Derivatives
  • Alkanes and Alkenes
  • Acetates
  • Lactones
  • Cyclopropane and Derivatives
  • Ethers
  • Bicyclohexanes
  • Heterocyclic compounds
  • Furans
  • Cyclohexenes and Derivatives
  • Ketones
Pharmacology
Indication For the prevention of pregnancy in women who elect an oral contraceptive.
Pharmacodynamics 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.
Mechanism of action Progestins 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.
Absorption Oral bioavailability is approximately 76%.
Volume of distribution Not Available
Protein binding 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.
Route of elimination Not Available
Half life 30 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms
Form Route Strength
Tablet Oral
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility 2.25e-03 g/l ALOGPS
logP 2.36 ALOGPS
logP 3.37 ChemAxon
logS -5.2 ALOGPS
pKa (strongest basic) -5 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 43.37 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 101.68 ChemAxon
polarizability 41.81 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. Pubmed
External Links
Resource Link
KEGG Drug D03917 Link_out
PubChem Compound 68873 Link_out
PubChem Substance 46507653 Link_out
ChemSpider 62105 Link_out
ChEBI 50838 Link_out
ChEMBL 50838 Link_out
Therapeutic Targets Database DAP001206 Link_out
PharmGKB PA164749409 Link_out
Drug Product Database 2261731 Link_out
Wikipedia http://en.wikipedia.org/wiki/Drospirenone Link_out
ATC Codes Not Available
AHFS Codes
  • 68:12
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Artemether Artemether may decrease the effectiveness of drospirinone by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
Benazepril Increased risk of hyperkalemia
Bexarotene Bexarotene 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).
Candesartan Increased risk of hyperkalemia
Captopril Increased risk of hyperkalemia
Cilazapril Increased risk of hyperkalemia
Colesevelam Bile 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.
Enalapril Increased risk of hyperkalemia
Eprosartan Increased risk of hyperkalemia
Fosinopril Increased risk of hyperkalemia
Heparin Heparin can increase risk of hyperkalemia for patients on drospirenone
Irbesartan Increased risk of hyperkalemia
Lisinopril Increased risk of hyperkalemia
Losartan Increased risk of hyperkalemia
Olmesartan Increased risk of hyperkalemia
Perindopril Increased risk of hyperkalemia
Potassium Increased risk of hyperkalemia
Quinapril Increased risk of hyperkalemia
Ramipril Increased risk of hyperkalemia
Telmisartan Telmisartan may increase the hyperkalemic effect of Drospirenone. Monitor for increased serum potassium concentrations during concomitant therapy.
Thiopental Thiopental may decrease the effect of Drospirenone. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.
Trandolapril Increased risk of hyperkalemia. Monitor serum potassium levels.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Tretinoin Oral Tretinoin may decrease the effect of oral contraceptive, Drospirenone. An alternate form of contraception should be used during concomitant therapy.
Triamterene Increased risk of hyperkalemia
Warfarin Drospirenone 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

Pharmacological action: yes
Actions: agonist

The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues

Organism class: human
UniProt ID: P06401 Link_out
Gene: PGR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: antagonist

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

Organism class: human
UniProt ID: P08235 Link_out
Gene: NR3C2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: antagonist

The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Activated, but not phosphorylated, by HIPK3

Organism class: human
UniProt ID: P10275 Link_out
Gene: AR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity

UniProt ID: P35354 Link_out
Gene: PTGS2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

An acylcholine + H(2)O = choline + a carboxylate

UniProt ID: P06276 Link_out
Gene: BCHE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on July 08, 2007 11:03 / Updated on February 08, 2013 16:20