Drospirenone

Drospirenone (DRSP) is a synthetic progestogen used in combined oral contraceptives and hormone replacement therapy. Unlike other progestins, DRSP is a spirolactone, instead of a progesterone or testosterone derivative.

Tags
Approvals
US FDA-Approved
drospirenone
MOL SDF CML

Identifiers

Abbreviation

DRSP

info

References

Names

1,2-dihydrospirorenone

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References

  1. Wikipedia: Drospirenone (View all citations for this reference)

CASRN

67392-87-4

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References

PubChem CID

68873

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References

  1. PubChem: Drospirenone (View all citations for this reference)

ECHA InfoCard

  • 100.060.599
  • EC / List #: 266-679-2

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References

  1. ECHA: Drospirenone (View all citations for this reference)

IUPHAR/BPS

2874

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References

  1. IUPHAR/BPS: Drospirenone (View all citations for this reference)

DrugBank Accession Number

DB01395

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References

  1. DrugBank: Drospirenone
    Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2017 Nov 8. doi: 10.1093/nar/gkx1037     (View all citations for this reference)

UNII

N295J34A25

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References

  1. UNII: Drospirenone (View all citations for this reference)

KEGG Entry Number

D03917

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References

  1. KEGG: Drospirenone (View all citations for this reference)

ChEBI ID

CHEBI:50838

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References

  1. ChEBI: Drospirenone (View all citations for this reference)

ChEMBL ID

CHEMBL1509

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References

  1. ChEMBL: Drospirenone (View all citations for this reference)

ChemSpider ID

62105

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References

  1. ChemSpider: Drospirenone (View all citations for this reference)

ATC Code(s)

info

Physical & Chemical Properties

Molecular Formula

C24H30O3

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References

Molecular Weight

366.50 g/mol

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References

Melting Point

USP: 198°-203° (dry over silica gel for at least 24 hours first)
IARC: 201.3 °C

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References

  1. United State Pharmacopoeia 40 (2017): Drospirenone monograph.
    2. (View all citations for this reference)
  2. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)
  3. Toxnet: Drospirenone (View all citations for this reference)
  4. Wang, Q.; Sun, Q. M.; Li, S. S.; Guo, L. Q.; Li, H. X-Ray Powder Diffraction Data for Drospirenone, C24H30O3. Powder Diffr. 2016, 31 (1), 63–65. (View all citations for this reference)

logP

4.02

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References

  1. Hazardous Substances Database: Drospirenone. (View all citations for this reference)

Specific Optical Rotation

USP: -187°-193° at 20° on anhydrous and solvent-free basis, 10 mg/mL in methanol
HSDB, IARC, Toxnet: -182° at 22° C/D (c = 0.5 in chloroform)

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References

  1. Hazardous Substances Database: Drospirenone. (View all citations for this reference)
  2. United State Pharmacopoeia 40 (2017): Drospirenone monograph.
    3. (View all citations for this reference)
  3. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)
  4. Toxnet: Drospirenone (View all citations for this reference)

Density

1.236 g/cm3

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References

  1. Wang, Q.; Sun, Q. M.; Li, S. S.; Guo, L. Q.; Li, H. X-Ray Powder Diffraction Data for Drospirenone, C24H30O3. Powder Diffr. 2016, 31 (1), 63–65. (View all citations for this reference)

Toxicology

GHS Hazard Code(s)

Class Category Code Description
Reproductive Toxicity 1B H360 May damage fertility or the unborn child
Acute Oral Toxicity 4 H302 Harmful if swallowed
Carcinogenicity 2 H351 Suspected of causing cancer if inhaled
Reproductive Toxicity 1A H360 May damage fertility or the unborn child
Reproductive Toxicity, Effects On or Via Lactation H362 May cause harm to breast-fed children

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References

  1. ECHA: Drospirenone (View all citations for this reference)

Mutagenicity

Not mutagenic in a number of tests: Ames, Chinese Hamster Lung gene mutation, human lymphocytes, mouse micronucleus.

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References

  1. Toxnet: Drospirenone (View all citations for this reference)

Genotoxicity

Not found to be genotoxic in human lymphocyte assay in vitro and mouse bone marrow micronucleus test in vivo.

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References

  1. (1) Reimann, R.; Kalweit, S.; Lang, R. Studies for a Genotoxic Potential of Some Endogenous and Exogenous Sex Steroids. II. Communication: Examination for the Induction of Cytogenetic Damage Using the Chromosomal Aberration Assay on Human Lymphocytes in Vitro and the Mouse Bone Marrow Micronucleus Test in vivo. Environ. Mol. Mutagen. 1996, 28 (2), 133–144. (View all citations for this reference)

Biochemistry & Pharmacology

Progesterone Receptor Activity

Agonist

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References

  1. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)

Androgen Receptor Activity

Partial antagonist (about 30% activity of cyproterone acetate)

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References

  1. Sitruk-Ware, R., New progestagens for contraceptive use. Hum. Reprod. Update 2006, 12 (2), 169-78.
    2. (View all citations for this reference)
  2. Su, Y.; Lian, Q. Q.; Ge, R. S., Contraceptives with novel benefits. Expert Opin Investig Drugs 2012, 21 (1), 83-90.
    3. (View all citations for this reference)
  3. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
    4. (View all citations for this reference)
  4. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
    5. (View all citations for this reference)
  5. Kuhl, H., Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005, 8 Suppl 1, 3-63.
    6. (View all citations for this reference)
  6. Sitruk-Ware, R.; Nath, A., The use of newer progestins for contraception. Contraception 2010, 82 (5), 410-7.
    7. (View all citations for this reference)
  7. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12e, 2011 > Estrogens and Progestins. Laurence L. Brunton, Bruce A. Chabner, Björn C. Knollmann.
    8. (View all citations for this reference)
  8. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)
  9. Krattenmacher, R. Drospirenone: Pharmacology and Pharmacokinetics of a Unique Progestogen. Contraception 2000, 62 (1), 29–38. (View all citations for this reference)

Estrogen Receptor Activity

Antagonist

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References

  1. Africander, D.; Verhoog, N.; Hapgood, J. P., Molecular mechanisms of steroid receptor-mediated actions by synthetic progestins used in HRT and contraception. Steroids 2011, 76 (7), 636-52.
    2. (View all citations for this reference)
  2. Kuhl, H., Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005, 8 Suppl 1, 3-63.
    3. (View all citations for this reference)
  3. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
    4. (View all citations for this reference)
  4. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
    5. (View all citations for this reference)
  5. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)

Glucocorticoid Receptor Activity

No activity

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References

  1. Kuhl, H., Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005, 8 Suppl 1, 3-63.
    2. (View all citations for this reference)
  2. Su, Y.; Lian, Q. Q.; Ge, R. S., Contraceptives with novel benefits. Expert Opin Investig Drugs 2012, 21 (1), 83-90.
    3. (View all citations for this reference)
  3. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
    4. (View all citations for this reference)
  4. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
    5. (View all citations for this reference)
  5. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)

Mineralocorticoid Receptor Activity

Antagonist (antimineralocorticoid or aldosterone antagonist). Agonist reports vary: "weak" (Africander) to "strong" (Bartsch).

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References

  1. Africander, D.; Verhoog, N.; Hapgood, J. P., Molecular mechanisms of steroid receptor-mediated actions by synthetic progestins used in HRT and contraception. Steroids 2011, 76 (7), 636-52.
    2. (View all citations for this reference)
  2. Kuhl, H., Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005, 8 Suppl 1, 3-63.
    3. (View all citations for this reference)
  3. Bartsch, V., Gynaecological uses of dienogest alone and in combination with oestrogens. Journal of Medical Drug Reviews 2015, 5, 1-31.
    4. (View all citations for this reference)
  4. Su, Y.; Lian, Q. Q.; Ge, R. S., Contraceptives with novel benefits. Expert Opin Investig Drugs 2012, 21 (1), 83-90.
    5. (View all citations for this reference)
  5. Sitruk-Ware, R., New progestagens for contraceptive use. Hum. Reprod. Update 2006, 12 (2), 169-78.
    6. (View all citations for this reference)
  6. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
    7. (View all citations for this reference)
  7. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
    8. (View all citations for this reference)
  8. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12e, 2011 > Estrogens and Progestins. Laurence L. Brunton, Bruce A. Chabner, Björn C. Knollmann.
    9. (View all citations for this reference)
  9. Hatcher, Robert A. Contraceptive Technology. New York: Ardent Media, Inc, 2004. Print.
    10. (View all citations for this reference)
  10. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)
  11. Stanczyk, F. Z.; Archer, D. F.; Bhavnani, B. R., Ethinyl estradiol and 17 beta-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment. Contraception 2013, 87 (6), 706-727.
    12. (View all citations for this reference)
  12. Sitruk-Ware, R.; El-Etr, M., Progesterone and related progestins: potential new health benefits. Climacteric 2013, 16, 69-78.
    13. (View all citations for this reference)
  13. Wikipedia: Drospirenone (View all citations for this reference)

Bioavailability

76-85%

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References

  1. Kuhl, H., Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005, 8 Suppl 1, 3-63.
    2. (View all citations for this reference)
  2. Schindler, A. E.; Campagnoli, C.; Druckmann, R.; Huber, J.; Pasqualini, J. R.; Schweppe, K. W.; Thijssen, J. H. H., Classification and pharmacology of progestins. Maturitas 2003, 46, 7-16.
    3. (View all citations for this reference)
  3. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)
  4. Krattenmacher, R. Drospirenone: Pharmacology and Pharmacokinetics of a Unique Progestogen. Contraception 2000, 62 (1), 29–38. (View all citations for this reference)
  5. Toxnet: Drospirenone (View all citations for this reference)

Elimination Half-Life (t1/2)

25-33 h

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References

  1. Su, Y.; Lian, Q. Q.; Ge, R. S., Contraceptives with novel benefits. Expert Opin Investig Drugs 2012, 21 (1), 83-90.
    2. (View all citations for this reference)
  2. Stanczyk, F. Z., Pharmacokinetics and potency of progestins used for hormone replacement therapy and contraception. Rev. Endocr. Metab. Disord. 2002, 3 (3), 211-224. (View all citations for this reference)
  3. Krattenmacher, R. Drospirenone: Pharmacology and Pharmacokinetics of a Unique Progestogen. Contraception 2000, 62 (1), 29–38. (View all citations for this reference)
  4. Toxnet: Drospirenone (View all citations for this reference)

Serum Protein Binding

95-96% bound to serum albumin. No binding to SHBG or CBG.

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References

  1. Schindler, A. E.; Campagnoli, C.; Druckmann, R.; Huber, J.; Pasqualini, J. R.; Schweppe, K. W.; Thijssen, J. H. H., Classification and pharmacology of progestins. Maturitas 2003, 46, 7-16.
    2. (View all citations for this reference)
  2. Krattenmacher, R. Drospirenone: Pharmacology and Pharmacokinetics of a Unique Progestogen. Contraception 2000, 62 (1), 29–38. (View all citations for this reference)
  3. Toxnet: Drospirenone (View all citations for this reference)

Metabolism

At least 20 different metabolites observed in urine and feces. Metabolites generated independently of the cytochrome P450 system, with only minor metabolism by CYP3A4.

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References

  1. Krattenmacher, R. Drospirenone: Pharmacology and Pharmacokinetics of a Unique Progestogen. Contraception 2000, 62 (1), 29–38. (View all citations for this reference)
  2. Nanda, K.; Stuart, G. S.; Robinson, J.; Gray, A. L.; Tepper, N. K.; Gaffield, M. E. Drug Interactions between Hormonal Contraceptives and Antiretrovirals. AIDS 2017, 31 (7), 917–952. (View all citations for this reference)

Excretion

Excreted mostly as glucuronide and sulfate conjugates in urine and feces.

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References

  1. Krattenmacher, R. Drospirenone: Pharmacology and Pharmacokinetics of a Unique Progestogen. Contraception 2000, 62 (1), 29–38. (View all citations for this reference)

Cmax

60-87 ng/mL

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References

  1. Krattenmacher, R. Drospirenone: Pharmacology and Pharmacokinetics of a Unique Progestogen. Contraception 2000, 62 (1), 29–38. (View all citations for this reference)

Tmax

1-2 h

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References

  1. Schindler, A. E.; Campagnoli, C.; Druckmann, R.; Huber, J.; Pasqualini, J. R.; Schweppe, K. W.; Thijssen, J. H. H., Classification and pharmacology of progestins. Maturitas 2003, 46, 7-16.
    2. (View all citations for this reference)
  2. Su, Y.; Lian, Q. Q.; Ge, R. S., Contraceptives with novel benefits. Expert Opin Investig Drugs 2012, 21 (1), 83-90.
    3. (View all citations for this reference)
  3. Krattenmacher, R. Drospirenone: Pharmacology and Pharmacokinetics of a Unique Progestogen. Contraception 2000, 62 (1), 29–38. (View all citations for this reference)

Enzyme Interactions

Inhibits 3β-hydroxysteroid dehydrogenase type 2 (HSD)

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References

  1. Toit, R. L. D.; Perkins, M. S.; Snoep, J. L.; Storbeck, K. H.; Africander, D., Fourth-generation progestins inhibit 3β-hydroxysteroid dehydrogenase type 2 and modulate the biosynthesis of endogenous steroids. PLoS ONE 2016, 11, 1-24.
    2. (View all citations for this reference)

Metabolites

Name
Structure
Notes
Other Drospirenone Metabolites

At least 20 different metabolites have been found, many with sulfate and glucuronide conjugates.

Drospirenone, Acid Form
structure

One of 2 major plasma metabolites. Formed independently of the cytochrome P450 enzyme system.

4,5-Dihydrodrospirenone
structure

One of 2 major plasma metabolites. Formed independently of the cytochrome P450 enzyme system. Circulates as the sulfate conjugate.

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Impurities

Name
Structure
CASRN
Other Names & Identifiers
7-Chloromethyl 17-Epidrospirenone
structure

932388-89-1

  • BP Drospirenone Impurity H
  • 17-Hydroxy-7β-chloromethyl-15β,16β-methylene-3-oxo-17β-pregn-4-ene-21-carboxylic acid, γ-lactone
  • 3'-chloro-3',6-seco-17-epidrospirenone
  • 7β-(chloromethyl)-3-oxo-15α,16α-dihydro-3'H-cyclopropa[15,16]pregn-4-ene-21,17-carbolactone

7-Hydroxymethyl Drospirenone
structure

  • BP Drospirenone Impurity B
  • 17-hydroxy-7β-hydroxymethyl-15β,16β-methylene-3-oxo-17α-pregn-4-ene-21-carboxylic acid, γ-lactone
  • 7β-hydroxymethyl drospirenone derivative
  • 7β-(hydroxymethyl)-3-oxo-15α,16α-dihydro-3'H-cyclopropa[15,16]-17α-pregn-4-ene-21,17-carbolactone

17-Epidrospirenone
structure

90457-65-1

  • USP Drospirenone Related Compound A
  • BP Drospirenone Impurity E
  • 17-Hydroxy-6β,7β:15β,16β-dimethylene-3-oxo-17β-pregn-4-ene-21-carboxylic acid, γ-lactone
  • 3-oxo-6α,7α,15α,16α-tetrahydro-3'H,3''H-dicyclopropa[6,7:15,16]pregn-4-ene-21,17-carbolactone

5-Hydroxydrospirenone
structure

197721-70-3

  • 5β,17-Dihydroxy-6β,7β:15β,16β-dimethylene-3-oxo-17α-pregnan-211-carboxylic acid, γ-lactone

7-Chloromethyl Drospirenone
structure

932388-90-4

  • BP Drospirenone Impurity G
  • 17-Hydroxy-7β-chloromethyl-15β,16β-methylene-3-oxo-17α-pregn-4-ene-21-carboxylic acid, γ-lactone
  • 3'-chloro-3',6-secodrospirenone
  • 7β-(chloromethyl)-3-oxo-15α16α-dihydro-3'H-cyclopropa[15,16]-17α-pregn-4-ene-21,17-carbolactone

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US FDA-Approved Products

Name
Formulation
Status
ANDA #
Yaz
DROSPIRENONE: 3 mg ETHINYL ESTRADIOL: 0.02 mg Oral tablet

Prescription

021676, 021873, 022045

Yasmin
DROSPIRENONE: 3 mg ETHINYL ESTRADIOL: 0.03 mg 28 Oral tablets

Prescription

021098

Yaela
DROSPIRENONE: 3 mg ETHINYL ESTRADIOL: 0.03 mg 28 Oral tablets

Prescription

202015

Syeda
DROSPIRENONE: 3 mg ETHINYL ESTRADIOL: 0.03 mg 28 Oral tablets

Prescription

090114

Safyral
DROSPIRENONE: 3 mg, N/A ETHINYL ESTRADIOL: 0.03 mg, N/A LEVAMEFOLATE CALCIUM: 0.451 mg, 0.451 mg Oral tablet

Prescription

022574

View All (22)