Levonorgestrel (LNG) is a synthetic progestational hormone used in hormonal contraceptives and as a component in hormone replacement therapy. It is the biologically active form of the racemic mixture norgestrel.
Abbreviation
LNG
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Names
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CASRN
797-63-7
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PubChem CID
13109
ECHA InfoCard
IUPHAR/BPS
2881
DrugBank Accession Number
DB00367
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UNII
5W7SIA7YZW
Reaxys ID
6067808
KEGG Entry Number
D00950
Wikipedia Entry Name
Levonorgestrel
ChEBI ID
CHEBI:6443
ChEMBL ID
CHEMBL1389
ChemSpider ID
12560
ATC Code(s)
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Molecular Formula
C21H28O2
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Molecular Weight
312.45 g/mol
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Appearance
White, crystalline powder
Melting Point
USP: 232-239° C, but the range between start and end of melting does not exceed 4° C
IARC: 235-237 °C
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Solubility
Slightly soluble in ethanol (1 in 120), chloroform (1 in 15), diethyl ether (1 in 400) and dioxane
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logP
3.48
Specific Optical Rotation
USP: Between -30 and -35°, 20 mg/mL in chloroform
-32.4 °C in chloroform
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Vapor Pressure
3.92 x 10-10 mm Hg at 25° C (estimated)
Density
1.197 g/cm3
Storage Conditions
20 to 25° C (68 to 77° F). Preserve in well-closed, light-resistant containers.
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GHS Hazard Code(s)
Class | Category | Code | Description |
---|---|---|---|
Acute Dermal Toxicity | 4 | H312 | Harmful in contact with skin |
Acute Inhalation Toxicity | 4 | H332 | Harmful if inhaled |
Carcinogenicity | 2 | H351 | Suspected of causing cancer if inhaled |
Reproductive Toxicity | 1A | H360FD | May damage fertility. May damage the unborn child |
Reproductive Toxicity, Effects On or Via Lactation | H362 | May cause harm to breast-fed children | |
Acute Oral Toxicity | 4 | H302 | Harmful if swallowed |
Reproductive Toxicity | 1B | H360 | May damage fertility or the unborn child |
Side Effects
SIDER: Haemorrhage, vulvovaginitis, amenorrhoea, abdominal pain, fatigue, nausea, menometrorrhagia, abdominal pain lower, asthenia, ovarian cyst, dizziness, breast tenderness, headache, seborrhoeic dermatitis.
AHFS: Reported in 5% or more of women: abdominal pain, leukorrhea, headache, vaginitis, back pain, breast pain, acne, depression, hypertension, upper respiratory infection, nausea, nervousness, dysmenorrhea, weight increase, skin disorder, decreased libido, abnormal Pap smear, sinusitis.
Mutagenicity
Levonorgestrel was not found to be mutagenic or genotoxic in the Ames Assay, in vitro mammalian culture assays utilizing mouse lymphoma cells and Chinese hamster ovary cells, and in an in vivo micronucleus assay in mice.
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LD50
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Progesterone Receptor Activity
Agonist
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Androgen Receptor Activity
Agonist
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Estrogen Receptor Activity
Antagonist
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Glucocorticoid Receptor Activity
Conflicting reports: not active (Ruan, Lello), weakly effective (Nath), active (Bartsch), binds to GR (Jordan), low affinity (Africander)
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Mineralocorticoid Receptor Activity
Agonist with high relative binding affinity. Conflicting reports on antagonism: Ruan and Lello indicate not active, while Africander says some anti-mineralocorticoid activity in rat models.
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Target Pathways
Bioavailability
100%
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Metabolism
CYP3A4
Apparent Volume of Distribution
260 L (Healthy female volunteers under fasting conditions)
1.8 L/kg
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Cmax
14.1 +/- 7.7 ng/mL (adult females, single dose of Plan B [0.75 mg levonorgestrel] administered in the morning
7.5 +/- 3.8 ng/mL (adolescent females, single dose of Plan B [0.75 mg levonorgestrel] administered in the evening)
Tmax
1.6 +/- 0.7 h (adult females, single dose of Plan B [0.75 mg levonorgestrel] administered in the morning
1.5 +/- 0.7 h (adolescent females, single dose of Plan B [0.75 mg levonorgestrel] administered in the evening)
Elimination Half-Life (t1/2)
36 +/- 13 h at steady-state (Toxnet)
28 +/- 6.4 h (Toxnet)
24.4 +/- 5.3 h (adult females, one table of Plan B [0.75 mg levonorgestrel])
22.2 +/- 6.8 h (adolescent females, one table of Plan B [0.75 mg levonorgestrel])
Serum Protein Binding
47.5% bound to SHBG, 50% to serum albumin, 2.5% unbound
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Excretion
45% of LNG and metabolites excreted in the urine and 32% excreted in feces, mostly as glucuronide conjugates
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Clearance
7.7 +/- 2.7 L/h (Healthy female volunteers under fasting conditions)
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Enzyme Interactions
Inhibits 3-oxo-5-alpha-steroid 4-dehydrogenase 1, CYP19A1
Inhibition of Ovulation
0.05-0.1 mg/day
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Transformation of Endometrium
5-6 mg/cycle
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Menstrual Delay
0.25-1.0 mg/day
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Indications
For the treatment of menopausal and postmenopausal disorders and alone or in combination with other hormones as an oral contraceptive.
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Sulfate conjugate also present, as well as the sulfate conjugate of the 16α stereoisomer. Metabolite of both levonorgestrel and norgestrel.
1260525-53-8
19914-67-1
Prescription
206851