U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of LEVOTHYROXINE

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

HIDE SMILES / InChI

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

1.02738238E12
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

1.02738238E12
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
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
[Pregnancy (conception) in hyper- or hypothyroidism].
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
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
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.
Name Type Language
LEVOTHYROXINE
HSDB   USP-RS   VANDF   WHO-DD  
Common Name English
SYNTHETIC LEVOTHYROXINE
Common Name English
LEVOTHYROXINE [VANDF]
Common Name English
O-(4-HYDROXY-3,5-DIIODOPHENYL)-3,5-DIIODO-L-TYROSINE
Systematic Name English
LIOTHYRONINE SODIUM IMPURITY A [EP IMPURITY]
Common Name English
SK&F 1-6528
Code English
Levothyroxine [WHO-DD]
Common Name English
LEVOTHYROXINE [USP-RS]
Common Name English
LEVOTHYROXIN
Common Name English
L-THYROXINE
Common Name English
NSC-36397
Code English
THYROXINE, L-
Common Name English
3,5,3',5'-TETRAIODO-L-THYRONINE
Systematic Name English
T4
Common Name English
L-TYROSINE, O-(4-HYDROXY-3,5-DIIODOPHENYL)-3,5-DIIODO-
Systematic Name English
THYROXINE
MI  
Common Name English
(-)-3-(4-(4-HYDROXY-3,5-DIIODOPHENOXY)-3,5-DIIODOPHENYL)ALANINE
Systematic Name English
LEVOTHYROXINE [HSDB]
Common Name English
THYROXINE [MI]
Common Name English
Classification Tree Code System Code
LOINC 14921-1
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
LOINC 73557-1
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CFR 21 CFR 520.1248
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LOINC 27000-9
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LOINC 35228-6
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LOINC 14920-3
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LOINC 3024-7
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CFR 21 CFR 862.1685
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
WHO-ESSENTIAL MEDICINES LIST 18.8
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LOINC 83121-4
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LOINC 3028-8
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LOINC 83119-8
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WHO-ATC H03AA03
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NDF-RT N0000007632
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LIVERTOX 958
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LOINC 20451-1
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LOINC 6892-4
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LOINC 31145-6
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LOINC 31144-9
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LOINC 35226-0
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NCI_THESAURUS C1553
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LOINC 83120-6
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LOINC 70217-5
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NCI_THESAURUS C886
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LOINC 38506-2
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WHO-VATC QH03AA03
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LOINC 70152-4
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LOINC 53350-5
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CFR 21 CFR 862.1700
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LOINC 83122-2
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LOINC 3027-0
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CFR 21 CFR 862.1695
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LOINC 53349-7
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LOINC 3025-4
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LOINC 3026-2
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NDF-RT N0000175945
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
Code System Code Type Description
FDA UNII
Q51BO43MG4
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
CHEBI
305790
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
CAS
51-48-9
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
NCI_THESAURUS
C62080
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
DRUG BANK
DB00451
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
CHEBI
18332
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
NSC
36397
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
ChEMBL
CHEMBL1624
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
LACTMED
Levothyroxine
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
DRUG CENTRAL
2646
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
CHEBI
30660
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
HSDB
3108
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
ECHA (EC/EINECS)
200-101-1
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
EVMPD
SUB02917MIG
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
RXCUI
10582
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY RxNorm
CHEBI
58448
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
IUPHAR
2635
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
SMS_ID
100000086128
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
WIKIPEDIA
LEVOTHYROXINE
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
DAILYMED
Q51BO43MG4
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
MERCK INDEX
M10840
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY Merck Index
MESH
D013974
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
EPA CompTox
DTXSID8023214
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
EVMPD
SUB127246
Created by admin on Wed Jul 05 22:47:41 UTC 2023 , Edited by admin on Wed Jul 05 22:47:41 UTC 2023
PRIMARY
PUBCHEM
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
PRIMARY
RS_ITEM_NUM
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
PRIMARY