Identification

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Name
Levothyroxine
Accession Number
DB00451  (APRD00235, EXPT02993)
Type
Small Molecule
Groups
Approved
Description

Levothyroxine is a synthetically produced form of thyroxine, a major endogenous hormone secreted by the thyroid gland.13 Also known as L-thyroxine or the brand name product Synthroid, levothyroxine is used primarily to treat hypothyroidism, a condition where the thyroid gland is no longer able to produce sufficient quantities of the thyroid hormones T4 (tetraiodothyronine or thyroxine) and T3 (triiodothyronine or Liothyronine), resulting in diminished down-stream effects of these hormones. Without sufficient quantities of circulating thyroid hormones, symptoms of hypothyroidism begin to develop such as fatigue, increased heart rate, depression4, dry skin and hair, muscle cramps, constipation, weight gain, memory impairment, and poor tolerance to cold temperatures.14,10

In response to Thyroid Stimulating Hormone (TSH) release by the pituitary gland, a normally functioning thyroid gland will produce and secrete T4, which is then converted through deiodination (by type I or type II 5′-deiodinases)8 into its active metabolite T3. While T4 is the major product secreted by the thyroid gland, T3 exerts the majority of the physiological effects of the thyroid hormones; T4 and T3 have a relative potency of ~1:4 (T4:T3).13 T4 and T3 act on nearly every cell of the body, but have a particularly strong effect on the cardiac system.6 As a result, many cardiac functions including heart rate, cardiac output, and systemic vascular resistance are closely linked to thyroid status.7

Prior to the development of levothyroxine, Thyroid, porcine or desiccated thyroid, used to be the mainstay of treatment for hypothyroidism. However, this is no longer recommended for the majority of patients due to several clinical concerns including limited controlled trials supporting its use. Desiccated thyroid products contain a ratio of T4 to T3 of 4.2:1, which is significantly lower than the 14:1 ratio of secretion by the human thyroid gland. This higher proportion of T3 in desiccated thyroid products can lead to supraphysiologic levels of T3 which may put patients at risk of thyrotoxicosis if thyroid extract therapy is not adjusted according to the serum TSH.10,14

Structure
Thumb
Synonyms
  • 3,3',5,5'-Tetraiodo-L-thyronine
  • 3,5,3',5'-Tetraiodo-L-thyronine
  • 4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodo-L-phenylalanine
  • L-T4
  • L-Thyroxine
  • Levothyroxin
  • LT4
  • O-(4-Hydroxy-3,5-diidophenyl)-3,5-diiodo-L-tyrosine
  • O-(4-Hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosine
  • T4
Product Ingredients
IngredientUNIICASInChI Key
Levothyroxine sodium054I36CPMN55-03-8YDTFRJLNMPSCFM-UHFFFAOYSA-M
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EltroxinTabletOralAspen Pharmacare Canada Inc.1974-12-31Not applicableCanada
EltroxinTabletOralAspen Pharmacare Canada Inc.1998-11-27Not applicableCanada
EltroxinTabletOralAspen Pharmacare Canada Inc.1951-12-30Not applicableCanada
EltroxinTabletOralAspen Pharmacare Canada Inc.1997-04-02Not applicableCanada
EltroxinTabletOralAspen Pharmacare Canada Inc.1998-02-112018-09-17Canada
Eltroxin 150 TabTabletOralGlaxo Canada Inc1974-12-311999-08-12Canada
Eltroxin Tab 100mcgTabletOralGlaxo Canada Inc1951-12-311999-08-12Canada
Eltroxin Tab 200mcgTabletOralGlaxo Canada Inc1960-12-311998-07-30Canada
Eltroxin Tab 300mcgTabletOralGlaxo Canada Inc1966-12-311998-07-30Canada
Eltroxin Tab 50mcgTabletOralGlaxo Canada Inc1951-12-311998-07-30Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Levothroxine SodiumTablet75 ug/1OralDirect_Rx2019-07-03Not applicableUs
LevothyroxineTablet125 ug/1OralNorthwind Pharmaceuticals2014-09-14Not applicableUs00527 1347 10 nlmimage10 430821d1
Levothyroxine SodiumTablet100 ug/1OralA-S Medication Solutions2002-11-012018-04-18Us50090 088920180907 15195 5n67bd
Levothyroxine SodiumTablet125 ug/1OralPreferreed Pharmaceuticals Inc.2018-04-02Not applicableUs
Levothyroxine SodiumTablet50 ug/1OralMylan Institutional Inc.2007-02-05Not applicableUs
Levothyroxine sodiumTablet125 ug/1OralProficient Rx LP2002-03-01Not applicableUs
Levothyroxine SodiumTablet0.15 mg/1OralLupin Pharmaceuticals, Inc.2019-03-20Not applicableUs
Levothyroxine SodiumTablet25 ug/1OralMylan Pharmaceuticals Inc.2002-11-01Not applicableUs0378 180020180907 15195 23ubjb
Levothyroxine sodiumTablet100 ug/1OralNucare Pharmaceuticals,inc.2002-03-01Not applicableUs
Levothyroxine SodiumTablet88 ug/1OralDirect_Rx2019-09-06Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
ThyrolarLevothyroxine sodium (50 ug/1) + Liothyronine sodium (12.5 ug/1)TabletOralAllergan1969-11-21Not applicableUs
ThyrolarLevothyroxine sodium (25 ug/1) + Liothyronine sodium (6.25 ug/1)TabletOralAllergan1969-11-21Not applicableUs
ThyrolarLevothyroxine sodium (12.5 ug/1) + Liothyronine sodium (3.1 ug/1)TabletOralAllergan1969-11-21Not applicableUs
ThyrolarLevothyroxine sodium (150 ug/1) + Liothyronine sodium (37.5 ug/1)TabletOralAllergan1969-11-21Not applicableUs
ThyrolarLevothyroxine sodium (100 ug/1) + Liothyronine sodium (25 ug/1)TabletOralAllergan1969-11-21Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Levothyroxine and Liothyronine ThyroidLevothyroxine (76 ug/1) + Liothyronine (18 ug/1)TabletOralWestminster2017-11-15Not applicableUs
Levothyroxine and Liothyronine ThyroidLevothyroxine (38 ug/1) + Liothyronine (9 ug/1)TabletOralbryant ranch prepack2017-09-19Not applicableUs
Levothyroxine and Liothyronine ThyroidLevothyroxine (57 ug/1) + Liothyronine (13.5 ug/1)TabletOralWestminster2017-09-19Not applicableUs
Levothyroxine and Liothyronine ThyroidLevothyroxine (38 ug/1) + Liothyronine (9 ug/1)TabletOralWestminster2017-09-19Not applicableUs
Levothyroxine and Liothyronine ThyroidLevothyroxine (19 ug/1) + Liothyronine (4.5 ug/1)TabletOralWestminster2017-09-19Not applicableUs
Levothyroxine and Liothyronine ThyroidLevothyroxine (9.5 ug/1) + Liothyronine (2.25 ug/1)TabletOralWestminster2017-11-15Not applicableUs
Levothyroxine and Liothyronine ThyroidLevothyroxine (19 ug/1) + Liothyronine (4.5 ug/1)TabletOralbryant ranch prepack2017-09-19Not applicableUs
NP Thyroid 120Levothyroxine (76 ug/1) + Liothyronine (18 ug/1)TabletOralPreferreed Pharmaceuticals Inc.2017-10-12Not applicableUs
NP Thyroid 120Levothyroxine (76 ug/1) + Liothyronine (18 ug/1)TabletOralAcella Pharmaceuticals, LLC2017-06-12Not applicableUs
NP Thyroid 15Levothyroxine (9.5 ug/1) + Liothyronine (2.25 ug/1)TabletOralPreferreed Pharmaceuticals Inc.2017-10-12Not applicableUs
International/Other Brands
Eutirox (Merck) / Letrox (Berlin-Chemie) / Levaxin (Nycomed) / Levothyrox (Merck) / Oroxine (GlaxoSmithKline) / Thyrax (Merck)
Categories
UNII
Q51BO43MG4
CAS number
51-48-9
Weight
Average: 776.87
Monoisotopic: 776.686681525
Chemical Formula
C15H11I4NO4
InChI Key
XUIIKFGFIJCVMT-LBPRGKRZSA-N
InChI
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
IUPAC Name
(2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
SMILES
N[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C(O)=O

Pharmacology

Indication

Levothyroxine is indicated as replacement therapy in primary (thyroidal), secondary (pituitary) and tertiary (hypothalamic) congenital or acquired hypothyroidism. It is also indicated as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.

Associated Conditions
Pharmacodynamics

Oral levothyroxine is a synthetic hormone that exerts the same physiologic effect as endogenous T4, thereby maintaining normal T4 levels when a deficiency is present.

Levothyroxine has a narrow therapeutic index and is titrated to maintain a euthyroid state with TSH (thyroid stimulating hormone) within a therapeutic range of 0.4–4.0 mIU/L.10 Over- or under-treatment with levothyroxine may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function and glucose and lipid metabolism. The dose of levothyroxine should be titrated slowly and carefully and patients should be monitored for their response to titration to avoid these effects. TSH levels should be monitored at least yearly to avoid over-treating with levothyroxine which can result in hyperthyroidism (TSH <0.1mIU/L) and symptoms of increased heart rate, diarrhea, tremor, hypercalcemia, and weakness to name a few.14

As many cardiac functions including heart rate, cardiac output, and systemic vascular resistance are closely linked to thyroid status,7 over-treatment with levothyroxine may result in increases in heart rate, cardiac wall thickness, and cardiac contractility and may precipitate angina or arrhythmias, particularly in patients with cardiovascular disease and in elderly patients. In populations with any cardiac concerns, levothyroxine should be initiated at lower doses than those recommended in younger individuals or in patients without cardiac disease. Patients receiving concomitant levothyroxine and sympathomimetic agents should be monitored for signs and symptoms of coronary insufficiency. If cardiac symptoms develop or worsen, reduce the levothyroxine dose or withhold for one week and restart at a lower dose.14

Increased bone resorption and decreased bone mineral density may occur as a result of levothyroxine over-replacement, particularly in post-menopausal women. The increased bone resorption may be associated with increased serum levels and urinary excretion of calcium and phosphorous, elevations in bone alkaline phosphatase and suppressed serum parathyroid hormone levels. Administer the minimum dose of levothyroxine that achieves the desired clinical and biochemical response to mitigate this risk.

Addition of levothyroxine therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Carefully monitor glycemic control after starting, changing or discontinuing levothyroxine.

Mechanism of action

Levothyroxine is a synthetically prepared levo-isomer of the thyroid hormone thyroxine (T4, a tetra-iodinated tyrosine derivative) that acts as a replacement in deficiency syndromes such as hypothyroidism. T4 is the major hormone secreted from the thyroid gland and is chemically identical to the naturally secreted T4: it increases metabolic rate, decreases thyroid-stimulating hormone (TSH) production from the anterior lobe of the pituitary gland, and, in peripheral tissues, is converted to T3. Thyroxine is released from its precursor protein thyroglobulin through proteolysis and secreted into the blood where is it then peripherally deiodinated to form triiodothyronine (T3) which exerts a broad spectrum of stimulatory effects on cell metabolism. T4 and T3 have a relative potency of ~1:4.

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.

The thyroid hormones have been shown to exert both genomic and non-genomic effects.9 They exert their genomic effects by diffusing into the cell nucleus and binding to thyroid hormone receptors in DNA regions called thyroid hormone response elements (TREs) near genes.2 This complex of T4, T3, DNA, and other coregulatory proteins causes a conformational change and a resulting shift in transcriptional regulation of nearby genes, synthesis of messenger RNA, and cytoplasmic protein production.2,6 For example, in cardiac tissues T3 has been shown to regulate the genes for α- and β-myosin heavy chains, production of the sarcoplasmic reticulum proteins calcium-activated ATPase (Ca2+-ATPase) and phospholamban, β-adrenergic receptors, guanine-nucleotide regulatory proteins, and adenylyl cyclase types V and VI as well as several plasma-membrane ion transporters, such as Na+/K+–ATPase, Na+/Ca2+ exchanger, and voltage-gated potassium channels, including Kv1.5, Kv4.2, and Kv4.3. 7 As a result, many cardiac functions including heart rate, cardiac output, and systemic vascular resistance are closely linked to thyroid status.

The non-genomic actions of the thyroid hormones have been shown to occur through binding to a plasma membrane receptor integrin aVb3 at the Arg-Gly-Asp recognition site.12 From the cell-surface, T4 binding to integrin results in down-stream effects including activation of mitogen-activated protein kinase (MAPK; ERK1/2) and causes subsequent effects on cellular/nuclear events including angiogenesis and tumor cell proliferation.6,11

TargetActionsOrganism
AThyroid hormone receptor alpha
agonist
Humans
AThyroid hormone receptor beta
agonist
Humans
AIntegrin alpha-VNot AvailableHumans
AIntegrin beta-3Not AvailableHumans
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Absorption

Absorption of orally administered T4 from the gastrointestinal tract ranges from 40% to 80% with the majority of the levothyroxine dose absorbed from the jejunum and upper ileum. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybeans, milk, and dietary fiber. Absorption may also decrease with age. In addition, many drugs affect T4 absorption including bile acide sequestrants, sucralfate, proton pump inhibitors, and minerals such as calcium (including in yogurt and milk products)3, magnesium, iron, and aluminum supplements. To prevent the formation of insoluble chelates, levothyroxine should generally be taken on an empty stomach at least 2 hours before a meal and separated by at least 4 hours from any interacting agents.

Volume of distribution
Not Available
Protein binding

Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA) and albumin (TBA). The higher affinity of both TBG and TBPA for T4 partially explains the higher serum levels, slower metabolic clearance and longer half-life of T4 compared to T3. Protein-bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone where only unbound hormone is metabolically active.14

Metabolism

Approximately 70% of secreted T4 is deiodinated to equal amounts of T3 and reverse triiodothyronine (rT3), which is calorigenically inactive. T4 is slowly eliminated through its major metabolic pathway to T3 via sequential deiodination, where approximately 80% of circulating T3 is derived from peripheral T4. The liver is the major site of degradation for both T4 and T3, with T4 deiodination also occurring at a number of additional sites, including the kidney and other tissues.

Elimination of T4 and T3 involves hepatic conjugation to glucuronic and sulfuric acids. The hormones undergo enterohepatic circulation as conjugates are hydrolyzed in the intestine and reabsorbed. Conjugated compounds that reach the colon are hydrolyzed and eliminated as free compounds in the feces. Other minor T4 metabolites have been identified. 14

Route of elimination

Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces. Approximately 20% of T4 is eliminated in the stool. Urinary excretion of T4 decreases with age.14

Half life

T4 half-life is 6 to 7 days. T3 half-life is 1 to 2 days.14

Clearance
Not Available
Toxicity

LD50=20 mg/kg (orally in rat). Hypermetabolic state indistinguishable from thyrotoxicosis of endogenous origin. Symptoms of thyrotoxicosis include weight loss, increased appetite, palpitations, nervousness, diarrhea, abdominal cramps, sweating, tachycardia, increased pulse and blood pressure, cardiac arrhythmias, tremors, insomnia, heat intolerance, fever, and menstrual irregularities.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Thyroid Hormone SynthesisMetabolic
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe metabolism of Levothyroxine can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Levothyroxine can be decreased when combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Levothyroxine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Levothyroxine.
3-isobutyl-1-methyl-7H-xanthineLevothyroxine may increase the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a lower serum level and potentially a reduction in efficacy.
3,5-diiodothyropropionic acidThe metabolism of Levothyroxine can be decreased when combined with 3,5-diiodothyropropionic acid.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Levothyroxine.
4-hydroxycoumarinThe metabolism of Levothyroxine can be decreased when combined with 4-hydroxycoumarin.
5-androstenedioneThe metabolism of Levothyroxine can be decreased when combined with 5-androstenedione.
5-fluorouridineThe therapeutic efficacy of Levothyroxine can be decreased when used in combination with 5-fluorouridine.
Additional Data Available
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  • Severity
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Food Interactions
  • Absorption increased in fasting state and decreased in malabsorption states.
  • Consistent administration in relation to meals is recommended.
  • No iron or calium carbonate within 4 hours of taking this medication.
  • Oral administration with infant soybean formula, soybean flour, cotton seed meal, walnuts, foods containing large amounts of fiber, ferrous sulfate, and antacids may decrease drug absorption.
  • Take 30-60 minutes before breakfast.

References

Synthesis Reference

Jivn-Ren Chen, Dimitri C. Papadimitriou, "Stable dosage of levothyroxine sodium and process of production." U.S. Patent US5225204, issued November, 1991.

US5225204
General References
  1. Uchino H, Kanai Y, Kim DK, Wempe MF, Chairoungdua A, Morimoto E, Anders MW, Endou H: Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1): insights into the mechanisms of substrate recognition. Mol Pharmacol. 2002 Apr;61(4):729-37. [PubMed:11901210]
  2. Cheng SY, Leonard JL, Davis PJ: Molecular aspects of thyroid hormone actions. Endocr Rev. 2010 Apr;31(2):139-70. doi: 10.1210/er.2009-0007. Epub 2010 Jan 5. [PubMed:20051527]
  3. Chon DA, Reisman T, Weinreb JE, Hershman JM, Leung AM: Concurrent Milk Ingestion Decreases Absorption of Levothyroxine. Thyroid. 2018 Apr;28(4):454-457. doi: 10.1089/thy.2017.0428. Epub 2018 Mar 28. [PubMed:29589994]
  4. Tang R, Wang J, Yang L, Ding X, Zhong Y, Pan J, Yang H, Mu L, Chen X, Chen Z: Subclinical Hypothyroidism and Depression: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2019 Jun 4;10:340. doi: 10.3389/fendo.2019.00340. eCollection 2019. [PubMed:31214119]
  5. Gottwald-Hostalek U, Uhl W, Wolna P, Kahaly GJ: New levothyroxine formulation meeting 95-105% specification over the whole shelf-life: results from two pharmacokinetic trials. Curr Med Res Opin. 2017 Feb;33(2):169-174. doi: 10.1080/03007995.2016.1246434. Epub 2016 Oct 21. [PubMed:27718637]
  6. Osmak-Tizon L, Poussier M, Cottin Y, Rochette L: Non-genomic actions of thyroid hormones: Molecular aspects. Arch Cardiovasc Dis. 2014 Apr;107(4):207-11. doi: 10.1016/j.acvd.2014.02.001. Epub 2014 Mar 26. [PubMed:24680385]
  7. Klein I, Ojamaa K: Thyroid hormone and the cardiovascular system. N Engl J Med. 2001 Feb 15;344(7):501-9. doi: 10.1056/NEJM200102153440707. [PubMed:11172193]
  8. Kaplan MM, Breitbart R: Conversion of thyroxine to triiodothyronine in the anterior pituitary gland and the influence of this process on thyroid status. Horm Metab Res Suppl. 1984;14:79-85. [PubMed:6595194]
  9. Hammes SR, Davis PJ: Overlapping nongenomic and genomic actions of thyroid hormone and steroids. Best Pract Res Clin Endocrinol Metab. 2015 Aug;29(4):581-93. doi: 10.1016/j.beem.2015.04.001. Epub 2015 Apr 22. [PubMed:26303085]
  10. Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, Cooper DS, Kim BW, Peeters RP, Rosenthal MS, Sawka AM: Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014 Dec;24(12):1670-751. doi: 10.1089/thy.2014.0028. [PubMed:25266247]
  11. Davis PJ, Leonard JL, Davis FB: Mechanisms of nongenomic actions of thyroid hormone. Front Neuroendocrinol. 2008 May;29(2):211-8. doi: 10.1016/j.yfrne.2007.09.003. Epub 2007 Oct 5. [PubMed:17983645]
  12. Bergh JJ, Lin HY, Lansing L, Mohamed SN, Davis FB, Mousa S, Davis PJ: Integrin alphaVbeta3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis. Endocrinology. 2005 Jul;146(7):2864-71. doi: 10.1210/en.2005-0102. Epub 2005 Mar 31. [PubMed:15802494]
  13. FDA Label - levothyroxine [File]
  14. American Association of Clinical Endocrinologists (AACE): Clinical Practice Guidelines for Hypothyroidism in Adults [File]
External Links
Human Metabolome Database
HMDB0000248
KEGG Drug
D08125
KEGG Compound
C01829
PubChem Compound
5819
PubChem Substance
46507672
ChemSpider
5614
BindingDB
50301375
ChEBI
18332
ChEMBL
CHEMBL1624
Therapeutic Targets Database
DAP000083
PharmGKB
PA450221
Guide to Pharmacology
GtP Drug Page
HET
T44
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Levothyroxine
ATC Codes
H03AA01 — Levothyroxine sodium
AHFS Codes
  • 68:36.04 — Thyroid Agents
PDB Entries
1eta / 1etb / 1f86 / 1hk1 / 1hk2 / 1hk3 / 1hk4 / 1hk5 / 1ict / 1ie4
show 13 more
MSDS
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedOtherPrimary Hypothyroidism1
0Enrolling by InvitationPreventionRecurrent Pregnancy Losses1
1Active Not RecruitingOtherHealthy Volunteers1
1CompletedNot AvailableDrug Drug Interaction (DDI)1
1CompletedNot AvailableHealthy Volunteers4
1CompletedBasic SciencePharmacokinetics2
1CompletedTreatmentDiabetes Mellitus (DM) / Healthy Volunteers1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentIron Deficiency Anemia (IDA) / Subclinical Hypothyroidism1
1Not Yet RecruitingOtherHealthy Volunteers1
1, 2CompletedTreatmentBrain Death1
1, 2RecruitingOtherHealthy Volunteers1
2CompletedNot AvailableThyroid Diseases1
2CompletedTreatmentHypothyroidism1
2RecruitingTreatmentBiomarkers / Endocrine System Diseases / Hypothyroidism1
2TerminatedTreatmentNon-Alcoholic Fatty Liver Disease (NAFLD) / Type 2 Diabetes Mellitus1
2, 3Active Not RecruitingPreventionGraves' Disease1
2, 3CompletedTreatmentBipolar Disorder (BD)1
2, 3CompletedTreatmentSubclinical Hypothyroidism2
2, 3Not Yet RecruitingTreatmentHypothyroidism / Neoplasms / Postoperative Complications1
2, 3RecruitingTreatmentHypothyroidism1
3CompletedTreatmentChronic Kidney Disease (CKD) / Subclinical Hypothyroidism1
3CompletedTreatmentHypothyroxinemia1
3CompletedTreatmentHypothyroxinemia / Pregnancy / Subclinical Hypothyroidism1
3Not Yet RecruitingTreatmentTransient Hypothyroxinemia of Prematurity (THOP)1
3RecruitingTreatmentEuthyroid Females1
3Unknown StatusTreatmentDyslipidemias1
4Active Not RecruitingTreatmentEndocrine System Diseases / Hypothyroidism / Thyroid Diseases2
4Active Not RecruitingTreatmentHealthy Volunteers1
4Active Not RecruitingTreatmentPostsurgical Hypothyroidism / Thyroid Cancers1
4CompletedNot AvailableHypothyroidism1
4CompletedPreventionGraves´ Disease1
4CompletedTreatmentAtherosclerosis / Heart Failure / Thyroid Dysfunction2
4CompletedTreatmentBone Mineral Density / Fractures, Bone / Osteoporosis / Thyroid Dysfunction1
4CompletedTreatmentDepression / Subclinical Hypothyroidism1
4CompletedTreatmentEuthyroid Sick Syndromes1
4CompletedTreatmentGoiter, Nodular1
4CompletedTreatmentHypothyroidism2
4CompletedTreatmentMental Fatigue / Thyroid Dysfunction / Tiredness1
4CompletedTreatmentSubclinical Hypothyroidism1
4RecruitingNot AvailableHypothyroidism1
4RecruitingTreatmentHeart Failure / Subclinical Hyperthyroidism / Subclinical Hypothyroidism1
4RecruitingTreatmentHypothyroidism1
4RecruitingTreatmentHypothyroidism;Postablative1
4RecruitingTreatmentHypothyroidism / Myocardial Infarction1
4TerminatedSupportive CareBrain Dead Organ Donors1
4Unknown StatusBasic ScienceDiabetes Mellitus (DM) / Hypothyroidism1
4Unknown StatusTreatmentHeart Failure With Reduced Ejection Fraction (HFrEF) / Sub-clinical Hypothyroidism1
4WithdrawnPreventionSystemic Lupus Erythematosus (SLE)1
4WithdrawnTreatmentGoitre1
4WithdrawnTreatmentSubclinical hypothyroïdism1
Not AvailableActive Not RecruitingOtherSubclinical Hypothyroidism1
Not AvailableCompletedNot AvailableHypothyroidism2
Not AvailableCompletedNot AvailableRecurrent Goiter1
Not AvailableCompletedNot AvailableSubclinical Hypothyroidism1
Not AvailableCompletedBasic ScienceHypothyroidism1
Not AvailableCompletedBasic ScienceObesity, Morbid1
Not AvailableCompletedScreeningPregnancy Loss / Sub Clinical Hypothyroidism / Subclinical hypothyroïdism1
Not AvailableCompletedTreatmentAnxiety / Depression / Distress / Thyroid Cancers / Tiredness1
Not AvailableCompletedTreatmentCongenital Hypothyroidism1
Not AvailableCompletedTreatmentCongenital Hypothyroidism / Hypothyroidism1
Not AvailableCompletedTreatmentDown Syndrome (DS) / Subclinical Hypothyroidism1
Not AvailableCompletedTreatmentHypothyroidism / Pregnancy1
Not AvailableCompletedTreatmentPregnancy / Thyroid Diseases1
Not AvailableCompletedTreatmentThyroid Nodules1
Not AvailableEnrolling by InvitationNot AvailableHead and Neck Carcinoma / Hypothyroidism; Surgery / Laryngeal Cancer / Laryngeal fistula / Wound Heal1
Not AvailableNot Yet RecruitingTreatmentHemodialysis Treatment / Hypothyroidism / Thyroid; Functional Disturbance1
Not AvailableRecruitingNot AvailableHypothyroidism1
Not AvailableRecruitingNot AvailableHypothyroidism / Postsurgical Hypothyroidism1
Not AvailableRecruitingNot AvailableQuality of Life / Thyroid; Deficiency1
Not AvailableRecruitingTreatmentASCVD / Dyslipidemias / Lipid-Lowering Therapy / Statin / Subclinical hypothyroïdism1
Not AvailableRecruitingTreatmentChronic Kidney Disease (CKD) / Thyroid Diseases1
Not AvailableRecruitingTreatmentHypothyroidism1
Not AvailableRecruitingTreatmentPregnancy Related / Thyroid1
Not AvailableTerminatedBasic ScienceHypothyroidism1
Not AvailableTerminatedTreatmentHypothyroidism / Neoplasms, Brain1
Not AvailableUnknown StatusDiagnosticCentral Hypothyroidism1
Not AvailableUnknown StatusTreatmentPrimary Hypothyroidism1

Pharmacoeconomics

Manufacturers
  • Institute biochimique sa (ibsa)
  • Institut biochimique sa ibsa
  • Vintage pharmaceuticals llc
  • Alara pharmaceutical corporation
  • Lloyd inc
  • Merck kgaa
  • Mylan pharmaceuticals inc
  • King pharmaceuticals inc
  • Abbott laboratories
  • Jerome stevens pharmaceuticals inc
Packagers
  • Abbott Laboratories Ltd.
  • Advanced Pharmaceutical Services Inc.
  • Akrimax Pharmaceuticals
  • Amerisource Health Services Corp.
  • Apotheca Inc.
  • APP Pharmaceuticals
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • BASF Corp.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bryant Ranch Prepack
  • Cardinal Health
  • Caremark LLC
  • Comprehensive Consultant Services Inc.
  • Corepharma LLC
  • Direct Dispensing Inc.
  • Direct Pharmaceuticals Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Forest Pharmaceuticals
  • Genpharm LP
  • Giant Food Inc.
  • H.E. Butt Grocery Co.
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Innovative Manufacturing and Distribution Services Inc.
  • Jerome Stevens Pharmaceuticals Inc.
  • JMI Daniels Pharmaceuticals Inc.
  • Kaiser Foundation Hospital
  • King Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Lannett Co. Inc.
  • Liberty Pharmaceuticals
  • Lloyd Pharmaceuticals
  • Macnary Ltd.
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Medisca Inc.
  • Merck KGaA
  • Monarch Pharmacy
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Neuman Distributors Inc.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Patheon Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmacy Service Center
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescript Pharmaceuticals
  • Qualitest
  • Rebel Distributors Corp.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Rite Aid Corp.
  • Sandhills Packaging Inc.
  • Sandoz
  • Simildiet SL
  • Southwood Pharmaceuticals
  • Stat Scripts LLC
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Va Cmop Dallas
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
InjectionIntravenous100 ug/5mL
InjectionIntravenous500 ug/5mL
Injection, powder, lyophilized, for solutionIntravenous100 ug/5mL
Injection, powder, lyophilized, for solutionIntravenous100 ug/1
Injection, powder, lyophilized, for solutionIntravenous200 ug/5mL
Injection, powder, lyophilized, for solutionIntravenous500 ug/1
Injection, powder, lyophilized, for solutionIntravenous500 ug/5mL
Injection, solutionIntravenous100 ug/1mL
Injection, solutionIntravenous20 ug/1mL
Injection, solutionIntravenous40 ug/1mL
TabletNot applicable100 ug/1
TabletNot applicable112 ug/1
TabletNot applicable125 ug/1
TabletNot applicable137 ug/1
TabletNot applicable150 ug/1
TabletNot applicable175 ug/1
TabletNot applicable200 ug/1
TabletNot applicable25 ug/1
TabletNot applicable50 ug/1
TabletNot applicable75 ug/1
TabletNot applicable88 ug/1
TabletOral.025 mg/1
TabletOral.05 mg/1
TabletOral.075 mg/1
TabletOral.088 mg/1
TabletOral.1 mg/1
TabletOral.112 mg/1
TabletOral.125 mg/1
TabletOral.137 mg/1
TabletOral.15 mg/1
TabletOral.150 mg/1
TabletOral0.025 mg/1
TabletOral0.05 mg/1
TabletOral0.050 mg/1
TabletOral0.075 mg/1
TabletOral0.088 mg/1
TabletOral0.1 mg/1
TabletOral0.100 mg/1
TabletOral0.112 mg/1
TabletOral0.125 mg/1
TabletOral0.137 mg/1
TabletOral0.15 mg/1
TabletOral0.150 mg/1
TabletOral0.175 mg/1
TabletOral0.2 mg/1
TabletOral0.200 mg/1
TabletOral0.3 mg/1
TabletOral0.300 mg/1
TabletOral100 ug/1
TabletOral112 ug/1
TabletOral125 ug/1
TabletOral137 ug/1
TabletOral150 ug/1
TabletOral175 ug/1
TabletOral200 ug/1
TabletOral25 ug/1
TabletOral300 ug/1
TabletOral50 ug/1
TabletOral75 ug/1
TabletOral88 ug/1
Powder, for solutionIntramuscular; Intravenous
TabletTopical
TabletOral100 mcg
TabletOral112 mcg
TabletOral125 mcg
TabletOral137 mcg
TabletOral150 mcg
TabletOral175 mcg
TabletOral200 mcg
TabletOral25 mcg
TabletOral300 mcg
TabletOral50 mcg
TabletOral75 mcg
TabletOral88 mcg
LiquidIntravenous
TabletOral
TabletOral
CapsuleOral100 ug/1
CapsuleOral112 ug/1
CapsuleOral125 ug/1
CapsuleOral13 ug/1
CapsuleOral137 ug/1
CapsuleOral150 ug/1
CapsuleOral175 ug/1
CapsuleOral200 ug/1
CapsuleOral25 ug/1
CapsuleOral50 ug/1
CapsuleOral75 ug/1
CapsuleOral88 ug/1
SolutionOral100 ug/1mL
SolutionOral112 ug/1mL
SolutionOral125 ug/1mL
SolutionOral13 ug/1mL
SolutionOral137 ug/1mL
SolutionOral150 ug/1mL
SolutionOral175 ug/1mL
SolutionOral200 ug/1mL
SolutionOral25 ug/1mL
SolutionOral50 ug/1mL
SolutionOral75 ug/1mL
SolutionOral88 ug/1mL
Prices
Unit descriptionCostUnit
Levothyroxine sodium powder159.12USD g
Levothyroxine 200 mcg vial24.0USD vial
Levothyroxine 500 mcg vial24.0USD vial
Levoxyl 300 mcg tablet2.34USD tablet
Synthroid 300 mcg tablet1.29USD tablet
Synthroid 175 mcg tablet1.07USD tablet
Synthroid 200 mcg tablet0.99USD tablet
Synthroid 137 mcg tablet0.87USD tablet
Synthroid 112 mcg tablet0.84USD tablet
Synthroid 125 mcg tablet0.84USD tablet
Synthroid 150 mcg tablet0.83USD tablet
Levothyroxine Sodium 300 mcg tablet0.77USD tablet
Synthroid 100 mcg tablet0.73USD tablet
Synthroid 75 mcg tablet0.72USD tablet
Synthroid 88 mcg tablet0.71USD tablet
Levoxyl 200 mcg tablet0.7USD tablet
Levoxyl 175 mcg tablet0.69USD tablet
Unithroid 300 mcg tablet0.69USD tablet
Synthroid 50 mcg tablet0.65USD tablet
Levoxyl 137 mcg tablet0.62USD tablet
Unithroid 200 mcg tablet0.62USD tablet
Levoxyl 112 mcg tablet0.61USD tablet
Synthroid 25 mcg tablet0.61USD tablet
Unithroid 175 mcg tablet0.61USD tablet
Levoxyl 150 mcg tablet0.59USD tablet
Levoxyl 125 mcg tablet0.58USD tablet
Levothyroxine Sodium 175 mcg tablet0.57USD tablet
Levothyroxine Sodium 200 mcg tablet0.57USD tablet
Levothyroxine 175 mcg tablet0.55USD tablet
Unithroid 150 mcg tablet0.55USD tablet
Levoxyl 88 mcg tablet0.54USD tablet
Unithroid 112 mcg tablet0.53USD tablet
Unithroid 125 mcg tablet0.53USD tablet
Levoxyl 75 mcg tablet0.52USD tablet
Levothroid 300 mcg tablet0.51USD tablet
Levoxyl 100 mcg tablet0.51USD tablet
Levothyroxine Sodium 100 mcg tablet0.5USD tablet
Levothyroxine Sodium 150 mcg tablet0.5USD tablet
Levothyroxine Sodium 88 mcg tablet0.5USD tablet
Levoxyl 50 mcg tablet0.49USD tablet
Unithroid 88 mcg tablet0.49USD tablet
Unithroid 100 mcg tablet0.47USD tablet
Unithroid 75 mcg tablet0.47USD tablet
Levothyroxine Sodium 125 mcg tablet0.47USD tablet
Levothyroxine Sodium 137 mcg tablet0.47USD tablet
Levothyroxine Sodium 50 mcg tablet0.47USD tablet
Levothyroxine Sodium 75 mcg tablet0.47USD tablet
Levothyroxine Sodium 112 mcg tablet0.46USD tablet
Levothyroxine 137 mcg tablet0.45USD tablet
Levoxyl 25 mcg tablet0.45USD tablet
Levothyroxine 112 mcg tablet0.44USD tablet
Levothyroxine Sodium 25 mcg tablet0.43USD tablet
Unithroid 50 mcg tablet0.43USD tablet
Unithroid 25 mcg tablet0.42USD tablet
Unithroid direct 100 mcg tablet0.42USD tablet
Unithroid direct 112 mcg tablet0.42USD tablet
Unithroid direct 125 mcg tablet0.42USD tablet
Unithroid direct 150 mcg tablet0.42USD tablet
Unithroid direct 175 mcg tablet0.42USD tablet
Unithroid direct 200 mcg tablet0.42USD tablet
Unithroid direct 25 mcg tablet0.42USD tablet
Unithroid direct 300 mcg tablet0.42USD tablet
Unithroid direct 50 mcg tablet0.42USD tablet
Unithroid direct 75 mcg tablet0.42USD tablet
Unithroid direct 88 mcg tablet0.42USD tablet
Levothroid 200 mcg tablet0.4USD tablet
Levothroid 175 mcg tablet0.38USD tablet
Levothyroxine 88 mcg tablet0.38USD tablet
Levothroid 125 mcg tablet0.36USD tablet
Levothroid 150 mcg tablet0.36USD tablet
Levothroid 100 mcg tablet0.35USD tablet
Levothroid 137 mcg tablet0.35USD tablet
Levothroid 112 mcg tablet0.34USD tablet
Levothroid 75 mcg tablet0.33USD tablet
Levothroid 88 mcg tablet0.33USD tablet
Levothyroxine 300 mcg tablet0.32USD tablet
Levothroid 25 mcg tablet0.31USD tablet
Unithroid 137 mcg tablet0.31USD tablet
Levothroid 50 mcg tablet0.3USD tablet
Levothyroxine 200 mcg tablet0.29USD tablet
Levothyroxine 150 mcg tablet0.24USD tablet
Levothyroxine 125 mcg tablet0.22USD tablet
Levothyroxine 100 mcg tablet0.2USD tablet
Levothyroxine 75 mcg tablet0.2USD tablet
Levothyroxine 50 mcg tablet0.18USD tablet
Synthroid 0.137 mg Tablet0.18USD tablet
Levothyroxine 25 mcg tablet0.17USD tablet
Synthroid 0.3 mg Tablet0.12USD tablet
Synthroid 0.175 mg Tablet0.11USD tablet
Synthroid 0.075 mg Tablet0.1USD tablet
Synthroid 0.088 mg Tablet0.1USD tablet
Synthroid 0.112 mg Tablet0.1USD tablet
Synthroid 0.125 mg Tablet0.1USD tablet
Synthroid 0.025 mg Tablet0.09USD tablet
Synthroid 0.2 mg Tablet0.09USD tablet
Synthroid 0.1 mg Tablet0.08USD tablet
Synthroid 0.15 mg Tablet0.08USD tablet
Eltroxin 0.3 mg Tablet0.07USD tablet
Synthroid 0.05 mg Tablet0.06USD tablet
Eltroxin 0.2 mg Tablet0.05USD tablet
Eltroxin 0.1 mg Tablet0.04USD tablet
Eltroxin 0.15 mg Tablet0.04USD tablet
Eltroxin 0.05 mg Tablet0.03USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7723390No2010-05-252024-03-14Us
US7101569No2006-09-052023-10-02Us
US7067148No2006-06-272022-02-15Us
US6555581No2003-04-292022-02-15Us
US6399101No2002-06-042020-03-30Us
US9168239No2015-10-272032-08-29Us
US9168238No2015-10-272032-08-29Us
US9006289No2015-04-142032-10-03Us
US7691411No2010-04-062024-03-14Us
US9782376No2017-10-102036-12-01Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)235.5 °CPhysProp
water solubility0.105 mg/mLNot Available
logP4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00898 mg/mLALOGPS
logP1.15ALOGPS
logP3.73ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)0.27ChemAxon
pKa (Strongest Basic)9.43ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area92.78 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity126.79 m3·mol-1ChemAxon
Polarizability49.4 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7212
Blood Brain Barrier-0.6886
Caco-2 permeable-0.653
P-glycoprotein substrateNon-substrate0.5321
P-glycoprotein inhibitor INon-inhibitor0.9175
P-glycoprotein inhibitor IINon-inhibitor0.9709
Renal organic cation transporterNon-inhibitor0.8891
CYP450 2C9 substrateNon-substrate0.8309
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6847
CYP450 1A2 substrateNon-inhibitor0.5924
CYP450 2C9 inhibitorNon-inhibitor0.7037
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8459
Ames testNon AMES toxic0.7591
CarcinogenicityNon-carcinogens0.9148
BiodegradationNot ready biodegradable0.9693
Rat acute toxicity2.7082 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9697
hERG inhibition (predictor II)Non-inhibitor0.8508
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
MS/MS Spectrum - Quattro_QQQ 10V, PositiveLC-MS/MSsplash10-0ac9-0591664310-c9b7aec3184ebb20a2da
MS/MS Spectrum - Quattro_QQQ 25V, PositiveLC-MS/MSsplash10-014i-2566449540-35bb942c7bcbcfe41af7
MS/MS Spectrum - Quattro_QQQ 40V, PositiveLC-MS/MSsplash10-00xr-3375497520-9dee3cb0c153e6c6df9e
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0059-0001001900-83ff4aafed0b73c6c7b7
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylalanine and derivatives. These are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Phenylalanine and derivatives
Alternative Parents
Diphenylethers / Phenylpropanoic acids / Diarylethers / Amphetamines and derivatives / L-alpha-amino acids / Phenoxy compounds / Phenol ethers / O-iodophenols / Aralkylamines / Iodobenzenes
show 10 more
Substituents
Phenylalanine or derivatives / Diphenylether / Diaryl ether / 3-phenylpropanoic-acid / Alpha-amino acid / Amphetamine or derivatives / L-alpha-amino acid / Phenoxy compound / Phenol ether / 2-halophenol
show 27 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
non-proteinogenic L-alpha-amino acid, L-phenylalanine derivative, iodophenol, 2-halophenol, thyroxine (CHEBI:18332) / thyroxine, Other amino acids, Biogenic amines (C01829)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Isoform Alpha-1: Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.Isoform Al...
Gene Name
THRA
Uniprot ID
P10827
Uniprot Name
Thyroid hormone receptor alpha
Molecular Weight
54815.055 Da
References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  3. Bernal J: Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab. 2007 Mar;3(3):249-59. [PubMed:17315033]
  4. Nakajima Y, Yamada M, Horiguchi K, Satoh T, Hashimoto K, Tokuhiro E, Onigata K, Mori M: Resistance to thyroid hormone due to a novel thyroid hormone receptor mutant in a patient with hypothyroidism secondary to lingual thyroid and functional characterization of the mutant receptor. Thyroid. 2010 Aug;20(8):917-26. doi: 10.1089/thy.2009.0389. [PubMed:20615127]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  6. Cheng SY, Leonard JL, Davis PJ: Molecular aspects of thyroid hormone actions. Endocr Rev. 2010 Apr;31(2):139-70. doi: 10.1210/er.2009-0007. Epub 2010 Jan 5. [PubMed:20051527]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.
Gene Name
THRB
Uniprot ID
P10828
Uniprot Name
Thyroid hormone receptor beta
Molecular Weight
52787.16 Da
References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  2. Marazuela M, Nattero L, Moure D, Garcia-Polo I, Figueroa-Vega N, Guijarro C: Thyroid hormone resistance and pituitary enlargement after thyroid ablation in a woman on levothyroxine treatment. Thyroid. 2008 Oct;18(10):1119-23. doi: 10.1089/thy.2007.0375. [PubMed:18816177]
  3. Sivakumar T, Chaidarun S: Resistance to thyroid hormone in a patient with coexisting Graves' disease. Thyroid. 2010 Feb;20(2):213-6. doi: 10.1089/thy.2009.0175. [PubMed:20151830]
  4. Grasberger H, Ringkananont U, Croxson M, Refetoff S: Resistance to thyroid hormone in a patient with thyroid dysgenesis. Thyroid. 2005 Jul;15(7):730-3. [PubMed:16053391]
  5. Cheng SY, Leonard JL, Davis PJ: Molecular aspects of thyroid hormone actions. Endocr Rev. 2010 Apr;31(2):139-70. doi: 10.1210/er.2009-0007. Epub 2010 Jan 5. [PubMed:20051527]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
General Function
Voltage-gated calcium channel activity
Specific Function
The alpha-V (ITGAV) integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF...
Gene Name
ITGAV
Uniprot ID
P06756
Uniprot Name
Integrin alpha-V
Molecular Weight
116036.855 Da
References
  1. Hammes SR, Davis PJ: Overlapping nongenomic and genomic actions of thyroid hormone and steroids. Best Pract Res Clin Endocrinol Metab. 2015 Aug;29(4):581-93. doi: 10.1016/j.beem.2015.04.001. Epub 2015 Apr 22. [PubMed:26303085]
  2. Davis PJ, Leonard JL, Davis FB: Mechanisms of nongenomic actions of thyroid hormone. Front Neuroendocrinol. 2008 May;29(2):211-8. doi: 10.1016/j.yfrne.2007.09.003. Epub 2007 Oct 5. [PubMed:17983645]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
General Function
Virus receptor activity
Specific Function
Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Wil...
Gene Name
ITGB3
Uniprot ID
P05106
Uniprot Name
Integrin beta-3
Molecular Weight
87056.975 Da
References
  1. Hammes SR, Davis PJ: Overlapping nongenomic and genomic actions of thyroid hormone and steroids. Best Pract Res Clin Endocrinol Metab. 2015 Aug;29(4):581-93. doi: 10.1016/j.beem.2015.04.001. Epub 2015 Apr 22. [PubMed:26303085]
  2. Davis PJ, Leonard JL, Davis FB: Mechanisms of nongenomic actions of thyroid hormone. Front Neuroendocrinol. 2008 May;29(2):211-8. doi: 10.1016/j.yfrne.2007.09.003. Epub 2007 Oct 5. [PubMed:17983645]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [PubMed:15601807]
  2. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [PubMed:15304429]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Regulator
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Siegmund W, Altmannsberger S, Paneitz A, Hecker U, Zschiesche M, Franke G, Meng W, Warzok R, Schroeder E, Sperker B, Terhaag B, Cascorbi I, Kroemer HK: Effect of levothyroxine administration on intestinal P-glycoprotein expression: consequences for drug disposition. Clin Pharmacol Ther. 2002 Sep;72(3):256-64. [PubMed:12235446]
  2. Mitin T, Von Moltke LL, Court MH, Greenblatt DJ: Levothyroxine up-regulates P-glycoprotein independent of the pregnane X receptor. Drug Metab Dispos. 2004 Aug;32(8):779-82. doi: 10.1124/dmd.32.8.779. [PubMed:15258100]

Carriers

Details
1. Transthyretin
Kind
Protein
Organism
Humans
Pharmacological action
No
General Function
Identical protein binding
Specific Function
Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.
Gene Name
TTR
Uniprot ID
P02766
Uniprot Name
Transthyretin
Molecular Weight
15886.88 Da
References
  1. Eneqvist T, Lundberg E, Karlsson A, Huang S, Santos CR, Power DM, Sauer-Eriksson AE: High resolution crystal structures of piscine transthyretin reveal different binding modes for triiodothyronine and thyroxine. J Biol Chem. 2004 Jun 18;279(25):26411-6. Epub 2004 Apr 13. [PubMed:15082720]
  2. Palha JA: Transthyretin as a thyroid hormone carrier: function revisited. Clin Chem Lab Med. 2002 Dec;40(12):1292-300. [PubMed:12553433]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Major thyroid hormone transport protein in serum.
Gene Name
SERPINA7
Uniprot ID
P05543
Uniprot Name
Thyroxine-binding globulin
Molecular Weight
46324.12 Da
References
  1. Palha JA: Transthyretin as a thyroid hormone carrier: function revisited. Clin Chem Lab Med. 2002 Dec;40(12):1292-300. [PubMed:12553433]
Kind
Protein
Organism
Humans
Pharmacological action
No
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Palha JA: Transthyretin as a thyroid hormone carrier: function revisited. Clin Chem Lab Med. 2002 Dec;40(12):1292-300. [PubMed:12553433]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Thyroid hormone transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones thyroxine (T4) and rT3. Other potential substrates, such as triiodothyronine (T3), 17-beta-gluc...
Gene Name
SLCO1C1
Uniprot ID
Q9NYB5
Uniprot Name
Solute carrier organic anion transporter family member 1C1
Molecular Weight
78695.625 Da
References
  1. Westholm DE, Stenehjem DD, Rumbley JN, Drewes LR, Anderson GW: Competitive inhibition of organic anion transporting polypeptide 1c1-mediated thyroxine transport by the fenamate class of nonsteroidal antiinflammatory drugs. Endocrinology. 2009 Feb;150(2):1025-32. doi: 10.1210/en.2008-0188. Epub 2008 Oct 9. [PubMed:18845642]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
  3. Pizzagalli F, Hagenbuch B, Stieger B, Klenk U, Folkers G, Meier PJ: Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96. [PubMed:12351693]
  4. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [PubMed:22541068]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Very active and specific thyroid hormone transporter. Stimulates cellular uptake of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and diidothyronine. Does not transport Leu,...
Gene Name
SLC16A2
Uniprot ID
P36021
Uniprot Name
Monocarboxylate transporter 8
Molecular Weight
59510.86 Da
References
  1. Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ: Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem. 2003 Oct 10;278(41):40128-35. Epub 2003 Jul 18. [PubMed:12871948]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Siegmund W, Altmannsberger S, Paneitz A, Hecker U, Zschiesche M, Franke G, Meng W, Warzok R, Schroeder E, Sperker B, Terhaag B, Cascorbi I, Kroemer HK: Effect of levothyroxine administration on intestinal P-glycoprotein expression: consequences for drug disposition. Clin Pharmacol Ther. 2002 Sep;72(3):256-64. [PubMed:12235446]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [PubMed:11159893]
  2. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [PubMed:22541068]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [PubMed:11159893]
  2. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [PubMed:22541068]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [PubMed:11159893]
  2. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [PubMed:22541068]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Thyroid hormone transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as the thyroid hormones T3 (triiodo-L-thyronine), T4 (thyroxine) and rT3, and of estrone-3-sulfate and taurocholate.
Gene Name
SLCO4A1
Uniprot ID
Q96BD0
Uniprot Name
Solute carrier organic anion transporter family member 4A1
Molecular Weight
77192.505 Da
References
  1. Fujiwara K, Adachi H, Nishio T, Unno M, Tokui T, Okabe M, Onogawa T, Suzuki T, Asano N, Tanemoto M, Seki M, Shiiba K, Suzuki M, Kondo Y, Nunoki K, Shimosegawa T, Iinuma K, Ito S, Matsuno S, Abe T: Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12. [PubMed:11316767]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Organic anion transporter, capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate and cAMP. May participate in the regulation of membrane transport of ...
Gene Name
SLCO4C1
Uniprot ID
Q6ZQN7
Uniprot Name
Solute carrier organic anion transporter family member 4C1
Molecular Weight
78947.525 Da
References
  1. Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, Abe M, Satoh F, Unno M, Hishinuma T, Inui K, Ito S, Goto J, Abe T: Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3569-74. Epub 2004 Mar 1. [PubMed:14993604]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Peptide antigen binding
Specific Function
Sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Involved in cellular a...
Gene Name
SLC7A5
Uniprot ID
Q01650
Uniprot Name
Large neutral amino acids transporter small subunit 1
Molecular Weight
55009.62 Da
References
  1. Uchino H, Kanai Y, Kim DK, Wempe MF, Chairoungdua A, Morimoto E, Anders MW, Endou H: Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1): insights into the mechanisms of substrate recognition. Mol Pharmacol. 2002 Apr;61(4):729-37. [PubMed:11901210]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [PubMed:22541068]

Drug created on June 13, 2005 07:24 / Updated on September 23, 2019 04:11