Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C15H11I4NO4 |
Molecular Weight | 776.87 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
N[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C(O)=O
InChI
InChIKey=XUIIKFGFIJCVMT-LBPRGKRZSA-N
InChI=1S/C15H11I4NO4/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)/t12-/m0/s1
DescriptionSources: http://www.drugbank.ca/drugs/DB00451Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/dosage/levothyroxine.html
Sources: http://www.drugbank.ca/drugs/DB00451
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.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1860 Sources: http://www.drugbank.ca/drugs/DB00451 |
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Target ID: CHEMBL1947 Sources: http://www.drugbank.ca/drugs/DB00451 |
0.136 nM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Synthroid Approved UseLevothyroxine 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 Date1.02738238E12 |
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Primary | Synthroid Approved UseLevothyroxine 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 Date1.02738238E12 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
76.64 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30153382 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1764.14 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30153382 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.04% |
unknown, unknown |
LEVOTHYROXINE plasma | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse 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) Sources: Tachycardia (grade 1) |
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... |
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) Sources: Palpitations (below serious, 3 patients) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/15258100/ |
no | |||
no | ||||
weak | ||||
weak | ||||
yes [IC50 15.4 uM] | ||||
yes [IC50 3.3 uM] | ||||
yes [IC50 4.9 uM] | ||||
yes | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | ||||
yes | ||||
Sources: https://go.drugbank.com/drugs/DB00451 |
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Heart hypertrophy induced by levothyroxine aggravates ischemic lesions and reperfusion arrhythmias in rats. | 1997 Jan |
|
Assessing the role of ortho-substitution on polychlorinated biphenyl binding to transthyretin, a thyroxine transport protein. | 2000 Jan 1 |
|
Potent competitive interactions of some brominated flame retardants and related compounds with human transthyretin in vitro. | 2000 Jul |
|
Improved antibody coating protocol using a second antibody antiserum. Application to total thyroxin immunoassay. | 2001 |
|
Short- and long-term results of total vs subtotal thyroidectomies in the surgical treatment of Graves' disease. | 2001 |
|
A case of pulmonary metastatic thyroid cancer complicated with Graves' disease. | 2001 Apr |
|
Graves' disease presenting as elephantiasic pretibial myxedema and nodules of the hands. | 2001 Apr |
|
Plasma concentrations of persistent organochlorines in relation to thyrotropin and thyroid hormone levels in women. | 2001 Apr |
|
[Prescription of thyroid function tests in adults as a function of clinical circumstances and of patient management]. | 2001 Apr 14 |
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[Pregnancy (conception) in hyper- or hypothyroidism]. | 2001 Apr 14 |
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[Timely recognition and treatment of hypothyroidism in pregnant women: benefit for the child]. | 2001 Apr 14 |
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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 |
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Thyroid hormones and thyroid antibodies in infertile males. | 2001 Aug |
|
The role of thyroid hormone administration in potential organ donors. | 2001 Dec |
|
Efficacy of high therapeutic doses of iodine-131 in patients with differentiated thyroid cancer and detectable serum thyroglobulin. | 2001 Feb |
|
Identification of thyroglobulin in orbital tissues of patients with thyroid-associated ophthalmopathy. | 2001 Feb |
|
Daily migraine with visual aura associated with an occipital arteriovenous malformation. | 2001 Feb |
|
Effects of seasonality and fasting on the plasma leptin and thyroxin levels of the raccoon dog (Nyctereutes procyonoides) and the blue fox (Alopex lagopus). | 2001 Feb 1 |
|
By the way, doctor. For years, I've been taking the same dose of Synthroid for hypothyroidism, and recent tests place me in the normal range. However, I still have several symptoms of low thyroid--fatigue, difficulty losing weight, sensitivity to cold, and constipation. My doctor doesn't seem concerned with the symptoms, as long as my blood tests are normal. But I'm frustrated. Is there anything I can do? | 2001 Jan |
|
[Thyroid carcinoma. Diagnosis--nonoperative therapy--after care]. | 2001 Jan 11 |
|
Amantadine-induced cortical myoclonus. | 2001 Jan 23 |
|
Effect of glutathione (GSH) depletion on the serum levels of triiodothyronine (T3), thyroxine (T4), and T3/T4 ratio in allyl alcohol-treated male rats and possible protection with zinc. | 2001 Jan-Feb |
|
Serum thyrotropin in primary hypothyroidism: a reliable and accurate predictor of optimal daily levothyroxine dose. | 2001 Jan-Feb |
|
Thyroid hormone deficiency determines predisposition to catalepsy in rats. | 2001 Jul |
|
Association between weight gain, blood parameters, and thyroid hormones and the development of ascites syndrome in broiler chickens. | 2001 Jul |
|
Stimulated healing of recalcitrant wounds by topical application of enriched cell culture medium: a clinical report. | 2001 Jul |
|
What is going on with levothyroxine. | 2001 Jul 9 |
|
[Euthyroid Graves' disease (problems of diagnosis and treatment)]. | 2001 Jul-Aug |
|
Five-year mortality in men and women with atrial fibrillation. | 2001 Jun |
|
[Concentration of thyrotropic hormone and free thyroxin in children with Down's syndrome]. | 2001 Jun |
|
[High levels of carcinoembryonic antigen in a woman with hypothyroidism]. | 2001 Jun 2 |
|
Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. | 2001 Mar |
|
A randomized trial comparing levothyroxine with radioactive iodine in the treatment of sporadic nontoxic goiter. | 2001 Mar |
|
[Comparison of the effectiveness of two different dosages of levothyroxine-iodide combinations for the therapy of euthyroid diffuse goiter]. | 2001 Mar 2 |
|
[The changes of PCBs and PCDFs as well as symptoms in Yusho patients for 30 years]. | 2001 May |
|
The various effects of amiodarone on thyroid function. | 2001 May |
|
Effect of levothyroxine administration time on serum TSH in elderly patients. | 2001 May |
|
[Morphological characteristics of placenta and hormonal balance in hyperthyroidism of pregnancy]. | 2001 May-Jun |
|
Changes of plasma arginine-vasopressin level in patients with hyperthyroidism during treatment. | 2001 May-Jun |
|
Usefulness of recombinant human thyrotropin in the radiometabolic treatment of selected patients with thyroid cancer. | 2001 Nov |
|
Thyroid function test abnormalities in newly admitted psychiatric patients residing in an iodine-deficient area: patterns and clinical significance. | 2001 Oct |
|
Abbott files NDA, will continue to distribute synthroid. | 2001 Oct 1 |
|
Thyroid hormones modify susceptibility to lidocaine-kindling in rats. | 2001 Oct 19 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/levothyroxine.html
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25447738
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.
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18.8
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admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
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5819
Created by
admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
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1365000
Created by
admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
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ACTIVE MOIETY
METABOLITE ACTIVE (PARENT)
METABOLITE INACTIVE (PARENT)
PRODRUG (METABOLITE ACTIVE)