Desogestrel

Desogestrel (DSG) is a synthetic progestin and prodrug of etonogestrel (ENG), derived from testosterone and used in hormonal contraceptives. DSG is primarily used in oral contraceptives, while ENG is primarily used in implants and vaginal rings.

Tags
Approvals
WHO Prequalification US FDA-Approved
Related Compounds
Etonogestrel
desogestrel

Identifiers

Abbreviation

DSG

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References

Names

13-ethyl-11-methylene-18,19-dinor-17α-4- pregnen-20-yn-17-ol

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References

CASRN

54024-22-5

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References

PubChem CID

40973

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IUPHAR/BPS

7065

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KEGG Entry Number

DB00304

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Wikipedia Entry Name

Desogestrel

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ChEBI ID

CHEBI:4453

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ChEMBL ID

CHEMBL1533

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ChemSpider ID

37400

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Physical & Chemical Properties

Molecular Formula

C22H30O

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References

Molecular Weight

310.473 g/mol

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References

Storage Conditions

Stable at normal conditions.

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Toxicology

Side Effects

General progestin side effects: Abnormal uterine bleeding; breast enlargement, pain, or tenderness; unexpected or increased flow of breast milk; hot flashes; loss of sexual desires; dry mouth; unusual thirst; frequent urination; abdominal pain; cramping; nausea; loss of appetite; dizziness; headache; mood changes; insomnia; unusual tiredness or weakness; swelling in ankles or feet; unusual or rapid weight gain; skin rash; acne; loss or gain of hair; brown spots on skin; sudden changes in vision.

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Carcinogenicity

No treatment-related tumorigenic effects seen from administration of desogestrel only. Increase in mammary adenocarcinoma in female rats in the high-dose group compared to controls.

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Mutagenicity

Not associated with point mutations in the in vitro Ames test and to chromosomal aberrations in a micronucleus test in female rats.

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LD50

  • Mouse oral: > 2000 mg/kg
  • Rat oral: > 2000 mg/kg

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Biochemistry & Pharmacology

Bioavailability

76% as etonogestrel.

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References

  1. Grandi, G.; Cagnacci, A.; Volpe, A. Pharmacokinetic Evaluation of Desogestrel as a Female Contraceptive. Expert Opin. Drug Metab. Toxicol. 2014, 10 (1), 1–10. (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)

Serum Protein Binding

As etonogestrel: 58% to serum albumin, 38% to SHBG, 3.5% unbound. (Grandi)
32% to SHBG, 66% to albumin, 2% free. (Schindler)

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References

  1. Grandi, G.; Cagnacci, A.; Volpe, A. Pharmacokinetic Evaluation of Desogestrel as a Female Contraceptive. Expert Opin. Drug Metab. Toxicol. 2014, 10 (1), 1–10. (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)

Cmax

  • 640 pg/mL from oral administration of 75 μg desogestrel
  • 4273 +/- 830 ng/L from 30 μg ethinyl estradiol/150 μg desogestrel oral pill

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Tmax

< 2 h from multiple oral administration of 75 μg desogestrel (Grandi)
1.15 h (Schindler)

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References

  1. Grandi, G.; Cagnacci, A.; Volpe, A. Pharmacokinetic Evaluation of Desogestrel as a Female Contraceptive. Expert Opin. Drug Metab. Toxicol. 2014, 10 (1), 1–10. (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)

Inhibition of Ovulation

0.06 mg/day

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References

  1. Rebar, R. W.; Zeserson, K., CHARACTERISTICS OF THE NEW PROGESTOGENS IN COMBINATION ORAL-CONTRACEPTIVES. Contraception 1991, 44 (1), 1-10.
  2. (View all citations for this reference)

Transformation of Endometrium

2.5 mg/cycle

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References

  1. Rebar, R. W.; Zeserson, K., CHARACTERISTICS OF THE NEW PROGESTOGENS IN COMBINATION ORAL-CONTRACEPTIVES. Contraception 1991, 44 (1), 1-10.
  2. (View all citations for this reference)

Menstrual Delay

~0.25 (mg/day

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References

  1. Rebar, R. W.; Zeserson, K., CHARACTERISTICS OF THE NEW PROGESTOGENS IN COMBINATION ORAL-CONTRACEPTIVES. Contraception 1991, 44 (1), 1-10.
  2. (View all citations for this reference)

Metabolites

Name
Structure
Notes
structure

Lower Progesterone Receptor and Estrogen Receptor activity than etonogestrel.

Glucuronide and sulfate conjugates of desogestrel and some of its metabolites (3β-hydroxydesogestrel, 15β-hydroxydesogestrel) are also formed.

Impurities

Name
Structure
CASRN
Other Names & Identifiers
structure

54024-21-4

  • USP Desogestrel Related Compound D
  • BP Desogestrel Impurity C

structure

54048-10-1

  • USP Desogestrel Related Compound C
  • BP Desogestrel Impurity D
  • 13-Ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-17-ol-3-one

structure

70805-85-5

  • USP Desogestrel Related Compound B
  • BP Desogestrel Impurity E

structure

  • BP Desogestrel Impurity B
  • 11-methylene-19-nor-17α-pregn-4-en-20-yn-17-ol

structure

201360-82-9

  • USP Desogestrel Related Compound A
  • BP Desogestrel Impurity A
  • Desogestrel Δ3 Isomer

US FDA-Approved Products

Name
Formulation
Status
ANDA #
DESOGESTREL: 0.15 mg, N/A
ETHINYL ESTRADIOL: 0.02 mg, 0.01 mg
28 Oral Tablets

Prescription

209170

DESOGESTREL: 0.15 mg
ETHINYL ESTRADIOL: 0.03 mg
28 oral tablets

Prescription

207081

DESOGESTREL: 0.1 mg, 0.125 mg, 0.15 mg ETHINYL ESTRADIOL: 0.025 mg, 0.025 mg, 0.025 mg 28 oral tablets

Prescription

021090

DESOGESTREL: 0.15 mg, N/A ETHINYL ESTRADIOL: 0.02 mg, 0.01 mg 28 oral tablets

Prescription

202689

DESOGESTREL: 0.15 mg, N/A ETHINYL ESTRADIOL: 0.02 mg, 0.01 mg 28 oral tablets

Prescription

091346

WHO Prequalified Medicines

WHO Reference #
Name
Applicant
Formulation
RH049 (a)
DESOGESTREL: 150 μg
ETHINYL ESTRADIOL: 30 μg
Tablet
Placebo tablet: 0 mg
RH044 (a)
DESOGESTREL: 150 μg
ETHINYL ESTRADIOL: 30 μg
Tablet
Placebo tablet: 0 mg
RH037 (a)
DESOGESTREL: 0.150 mg
ETHINYL ESTRADIOL: 0.030 mg
Tablet
RH025 (a)
DESOGESTREL: 0.150 mg
ETHINYL ESTRADIOL: 0.030 mg
Placebo: 0 mg
Tablet