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Details

Stereochemistry ABSOLUTE
Molecular Formula C15H10I4NO4.Na.H2O
Molecular Weight 816.8671
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LEVOTHYROXINE SODIUM MONOHYDRATE

SMILES

O.[Na+].N[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C([O-])=O

InChI

InChIKey=ANMYAHDLKVNJJO-LTCKWSDVSA-M
InChI=1S/C15H11I4NO4.Na.H2O/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23;;/h1-2,4-5,12,21H,3,20H2,(H,22,23);;1H2/q;+1;/p-1/t12-;;/m0../s1

HIDE SMILES / InChI

Molecular Formula Na
Molecular Weight 22.9898
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula HO
Molecular Weight 17.0073
Charge -1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C15H11I4NO4
Molecular Weight 776.87
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/dosage/levothyroxine.html

Levothyroxine (T4) is a synthetically prepared levo isomer of thyroxine, the major hormone secreted from the thyroid gland. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine (T3) which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid hormone increases the metabolic rate of cells of all tissues in the body. In the fetus and newborn, thyroid hormone is important for the growth and development of all tissues including bones and the brain. In adults, thyroid hormone helps to maintain brain function, food metabolism, and body temperature, among other effects. The symptoms of thyroid deficiency relieved by levothyroxine include slow speech, lack of energy, weight gain, hair loss, dry thick skin and unusual sensitivity to cold. Levothyroxine acts like the endogenous thyroid hormone thyroxine (T4, a tetra-iodinated tyrosine derivative). In the liver and kidney, T4 is converted to T3, the active metabolite. In order to increase solubility, the thyroid hormones attach to thyroid hormone binding proteins, thyroxin-binding globulin, and thyroxin-binding prealbumin (transthyretin). Transport and binding to thyroid hormone receptors in the cytoplasm and nucleus then takes place. Thus by acting as a replacement for natural thyroxine, symptoms of thyroxine deficiency are relieved. Levothyroxine is used for use alone or in combination with antithyroid agents to treat hypothyroidism, goiter, chronic lymphocytic thyroiditis, myxedema coma, and stupor.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.136 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Synthroid

Approved Use

Levothyroxine tablets are used for the following indications: Hypothyroidism As replacement or supplemental therapy in congenital or acquired hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis. Specific indications include: primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) hypothyroidism and subclinical hypothyroidism. Primary hypothyroidism may result from functional deficiency, primary atrophy, partial or total congenital absence of the thyroid gland, or from the effects of surgery, radiation, or drugs, with or without the presence of goiter. Pituitary TSH Suppression In the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis), multinodular goiter and, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well differentiated thyroid cancer.

Launch Date

2002
Primary
Synthroid

Approved Use

Levothyroxine tablets are used for the following indications: Hypothyroidism As replacement or supplemental therapy in congenital or acquired hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis. Specific indications include: primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) hypothyroidism and subclinical hypothyroidism. Primary hypothyroidism may result from functional deficiency, primary atrophy, partial or total congenital absence of the thyroid gland, or from the effects of surgery, radiation, or drugs, with or without the presence of goiter. Pituitary TSH Suppression In the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis), multinodular goiter and, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well differentiated thyroid cancer.

Launch Date

2002
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
76.64 ng/mL
600 μg single, oral
dose: 600 μg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOTHYROXINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1764.14 ng × h/mL
600 μg single, oral
dose: 600 μg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOTHYROXINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.2 day
unknown, unknown
LEVOTHYROXINE serum
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
7.5 h
unknown, unknown
LEVOTHYROXINE serum
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.04%
unknown, unknown
LEVOTHYROXINE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
5.7 mg 1 times / day single, oral
Studied dose
Dose: 5.7 mg, 1 times / day
Route: oral
Route: single
Dose: 5.7 mg, 1 times / day
Sources:
healthy, 22 months
n = 1
Health Status: healthy
Age Group: 22 months
Sex: M
Population Size: 1
Sources:
Other AEs: Hypertension, Tachycardia...
Other AEs:
Hypertension (grade 1)
Tachycardia (grade 1)
Sources:
18 mg 1 times / day single, oral
Studied dose
Dose: 18 mg, 1 times / day
Route: oral
Route: single
Dose: 18 mg, 1 times / day
Sources:
healthy, 30 months
n = 1
Health Status: healthy
Age Group: 30 months
Sex: M
Population Size: 1
Sources:
Other AEs: Hyperthyroidism, Seizures...
Other AEs:
Hyperthyroidism
Seizures
Sources:
600 ug 1 times / day single, oral
Studied dose
Dose: 600 ug, 1 times / day
Route: oral
Route: single
Dose: 600 ug, 1 times / day
Sources:
healthy, mean age 35 years
n = 36
Health Status: healthy
Age Group: mean age 35 years
Sex: M+F
Population Size: 36
Sources:
Disc. AE: Alanine aminotransferase increased...
AEs leading to
discontinuation/dose reduction:
Alanine aminotransferase increased (2.8%)
Sources:
50 ug steady, oral (total daily dose)
Dose: 50 ug
Route: oral
Route: steady
Dose: 50 ug
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Graves Disease
Population Size: 30
Sources:
Other AEs: Atrial fibrillation, Palpitations...
Other AEs:
Atrial fibrillation (serious, 1 patient)
Palpitations (below serious, 3 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Hypertension grade 1
5.7 mg 1 times / day single, oral
Studied dose
Dose: 5.7 mg, 1 times / day
Route: oral
Route: single
Dose: 5.7 mg, 1 times / day
Sources:
healthy, 22 months
n = 1
Health Status: healthy
Age Group: 22 months
Sex: M
Population Size: 1
Sources:
Tachycardia grade 1
5.7 mg 1 times / day single, oral
Studied dose
Dose: 5.7 mg, 1 times / day
Route: oral
Route: single
Dose: 5.7 mg, 1 times / day
Sources:
healthy, 22 months
n = 1
Health Status: healthy
Age Group: 22 months
Sex: M
Population Size: 1
Sources:
Hyperthyroidism
18 mg 1 times / day single, oral
Studied dose
Dose: 18 mg, 1 times / day
Route: oral
Route: single
Dose: 18 mg, 1 times / day
Sources:
healthy, 30 months
n = 1
Health Status: healthy
Age Group: 30 months
Sex: M
Population Size: 1
Sources:
Seizures
18 mg 1 times / day single, oral
Studied dose
Dose: 18 mg, 1 times / day
Route: oral
Route: single
Dose: 18 mg, 1 times / day
Sources:
healthy, 30 months
n = 1
Health Status: healthy
Age Group: 30 months
Sex: M
Population Size: 1
Sources:
Alanine aminotransferase increased 2.8%
Disc. AE
600 ug 1 times / day single, oral
Studied dose
Dose: 600 ug, 1 times / day
Route: oral
Route: single
Dose: 600 ug, 1 times / day
Sources:
healthy, mean age 35 years
n = 36
Health Status: healthy
Age Group: mean age 35 years
Sex: M+F
Population Size: 36
Sources:
Palpitations below serious, 3 patients
50 ug steady, oral (total daily dose)
Dose: 50 ug
Route: oral
Route: steady
Dose: 50 ug
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Graves Disease
Population Size: 30
Sources:
Atrial fibrillation serious, 1 patient
50 ug steady, oral (total daily dose)
Dose: 50 ug
Route: oral
Route: steady
Dose: 50 ug
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Graves Disease
Population Size: 30
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Structure, evolution, and liver-specific expression of sterol 12alpha-hydroxylase P450 (CYP8B).
1999 Jul
Hypothyroidism presenting as hypercholesterolaemia and simvastatin-induced myositis.
2000 Dec
The role of selenocysteine 133 in catalysis by the human type 2 iodothyronine deiodinase.
2000 Dec
Thyroid function of former opioid addicts on naltrexone treatment.
2001
[A case of 'hallucination of soliloquy' with hypothyroidism induced Hashimoto disease. Meaning of psychopathological research about symptomatic psychosis].
2001
Short- and long-term results of total vs subtotal thyroidectomies in the surgical treatment of Graves' disease.
2001
Plasma concentrations of persistent organochlorines in relation to thyrotropin and thyroid hormone levels in women.
2001 Apr
Short-term hyperthyroidism followed by transient pituitary hypothyroidism in a very low birth weight infant born to a mother with uncontrolled Graves' disease.
2001 Apr
[Prescription of thyroid function tests in adults as a function of clinical circumstances and of patient management].
2001 Apr 14
[Timely recognition and treatment of hypothyroidism in pregnant women: benefit for the child].
2001 Apr 14
Development of hypertensive status in NISAG rats reared by normotensive Wistar rats.
2001 Aug
Hyperthyroidism affects lipid metabolism in lactating and suckling rats.
2001 Aug
Thyroid hormones and thyroid antibodies in infertile males.
2001 Aug
Developmental landmarks in offspring of rats exposed singly and in combination to Aroclor 1016 and levothyroxine.
2001 Aug
Coronary bypass surgery in patients with Sheehan's syndrome.
2001 Dec
Identification of thyroglobulin in orbital tissues of patients with thyroid-associated ophthalmopathy.
2001 Feb
Generic substitution: issues for problematic drugs.
2001 Jan
[Thyroid carcinoma. Diagnosis--nonoperative therapy--after care].
2001 Jan 11
Amantadine-induced cortical myoclonus.
2001 Jan 23
Age-related changes of protein- and RNA-synthetic processes in experimental hyper- and hypothyroidism.
2001 Jul
[High levels of carcinoembryonic antigen in a woman with hypothyroidism].
2001 Jun 2
Suppressive levothyroxine therapy has no significant influence on bone degradation in women with thyroid carcinoma: a comparison with other disorders affecting bone metabolism.
2001 Mar
One-year prophylactic treatment of euthyroid Hashimoto's thyroiditis patients with levothyroxine: is there a benefit?
2001 Mar
Disorders of growth and puberty in children with non-tumoral hydrocephalus.
2001 Mar
A randomized trial comparing levothyroxine with radioactive iodine in the treatment of sporadic nontoxic goiter.
2001 Mar
[Morphological characteristics of placenta and hormonal balance in hyperthyroidism of pregnancy].
2001 May-Jun
Use of soy protein supplement and resultant need for increased dose of levothyroxine.
2001 May-Jun
Treatment of hypothyroidism.
2001 Nov 15
Functional evidence for the presence of type II 5'-deiodinase in somatotropes and its adaptive role in hypothyroidism.
2001 Oct
Abbott files NDA, will continue to distribute synthroid.
2001 Oct 1
[Screening for thyroid disease. Occurrence of hypothyroidism and hyperthyroidism in patients admitted to a geriatric department].
2001 Oct 8
Acute aortic dissection associated with Sheehan's syndrome.
2001 Sep
Molecular cloning and sequence of Sparus aurata skeletal myosin light chains expressed in white muscle: developmental expression and thyroid regulation.
2001 Sep
[RTH syndrome--resistance to thyroid hormone syndrome].
2001 Sep 10
Patents

Sample Use Guides

Usual Adult Dose for Hypothyroidism Average full replacement dose: 1.7 mcg/kg/day (e.g., 100 to 125 mcg/day for a 70 kg adult) orally Older patients may require less than 1 mcg/kg/day
Route of Administration: Oral
Addition of Levothyroxine at concentrations of 100-200 nM rescued rat cerebellar granule neurons (CGNs) from cell death in K5 in a dose-dependent manner. 200 nM T4 was also effective in maintaining the neurites of CGNs in K5.
Substance Class Chemical
Created
by admin
on Sat Dec 16 00:10:00 GMT 2023
Edited
by admin
on Sat Dec 16 00:10:00 GMT 2023
Record UNII
B82379R9W0
Record Status Validated (UNII)
Record Version
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Name Type Language
LEVOTHYROXINE SODIUM MONOHYDRATE
WHO-IP  
Common Name English
LEVOTHYROXINUM NATRICUM MONOHYDRATE [WHO-IP LATIN]
Common Name English
L-TYROSINE, O-(4-HYDROXY-3,5-DIIODOPHENYL)-3,5-DIIODO-, MONOSODIUM SALT, MONOHYDRATE
Systematic Name English
LEVOTHYROXINE SODIUM MONOHYDRATE [WHO-IP]
Common Name English
Code System Code Type Description
PUBCHEM
23667619
Created by admin on Sat Dec 16 00:10:00 GMT 2023 , Edited by admin on Sat Dec 16 00:10:00 GMT 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
LEVOTHYROXINE SODIUM MONOHYDRATE
Created by admin on Sat Dec 16 00:10:00 GMT 2023 , Edited by admin on Sat Dec 16 00:10:00 GMT 2023
PRIMARY Description: An almost white or slightly coloured powder, or a fine, slightly coloured, crystalline powder; odourless. Solubility: Very slightly soluble in water; slightly soluble in ethanol (~750 g/L) TS; practically insoluble in acetone R and ether R. It dissolves in solutions of alkali hydroxides. Category: Thyroid hormone. Storage: Levothyroxine sodium should be kept in a tightly closed container, protected from light.Additional information: Levothyroxine sodium may contain a variable quantity of water of crystallization; anhydrous levothyroxine sodium is hygroscopic.Definition: Levothyroxine sodium contains not less than 97.0% and not more than 101.0% of C15H10I4NNaO4, calculated with reference to the dried substance.
CAS
31178-59-3
Created by admin on Sat Dec 16 00:10:00 GMT 2023 , Edited by admin on Sat Dec 16 00:10:00 GMT 2023
PRIMARY
FDA UNII
B82379R9W0
Created by admin on Sat Dec 16 00:10:00 GMT 2023 , Edited by admin on Sat Dec 16 00:10:00 GMT 2023
PRIMARY
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