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Liotrix

PubChem CID
71371
Structure
Liotrix_small.png
Molecular Formula
Synonyms
  • Liotrix
  • Euthroid
  • Combithyrex
  • Thyrolar
  • Diotroxin
Molecular Weight
1471.8 g/mol
Computed by PubChem 2.1 (PubChem release 2021.05.07)
Dates
  • Create:
    2005-06-24
  • Modify:
    2025-01-18
Description
Liotrix is a phenylalanine derivative.
Liotrix is a synthetically derived thyroid hormone replacement preparation. It consists of levothyroxine sodium (thyroxine, T4) and liothyronine sodium (triiodothyronine, T3) in a 4 to 1 ratio by weight. Liotrix was developed when it was believed that serum levels of both T4 and T3 were maintained by direct thyroidal secretion. It is now known that the thyroid gland secretes approximately ten times more T4 than T3 and that 80% of serum T3 is derived from deiodination of T4 in peripheral tissues. Administration of levothyroxine alone is sufficient for maintaining serum T4 and T3 levels in most patients and combination hormone replacement therapy generally offers no therapeutic advantage. In fact, administration of T3 may result in supratherapeutic levels of T3.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Liotrix.png

1.2 3D Status

Conformer generation is disallowed since MMFF94s unsupported element, mixture or salt

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

disodium;(2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoate;(2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoate
Computed by LexiChem 2.6.6 (PubChem release 2019.06.18)

2.1.2 InChI

InChI=1S/C15H11I4NO4.C15H12I3NO4.2Na/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;16-9-6-8(1-2-13(9)20)23-14-10(17)3-7(4-11(14)18)5-12(19)15(21)22;;/h1-2,4-5,12,21H,3,20H2,(H,22,23);1-4,6,12,20H,5,19H2,(H,21,22);;/q;;2*+1/p-2/t2*12-;;/m00../s1
Computed by InChI 1.0.5 (PubChem release 2019.06.18)

2.1.3 InChIKey

LKYWLLWWYBVUPP-XOCLESOZSA-L
Computed by InChI 1.0.5 (PubChem release 2019.06.18)

2.1.4 SMILES

C1=CC(=C(C=C1OC2=C(C=C(C=C2I)C[C@@H](C(=O)[O-])N)I)I)O.C1=C(C=C(C(=C1I)OC2=CC(=C(C(=C2)I)O)I)I)C[C@@H](C(=O)[O-])N.[Na+].[Na+]
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C30H21I7N2Na2O8
Computed by PubChem 2.1 (PubChem release 2019.06.18)

2.3 Other Identifiers

2.3.1 CAS

8065-29-0

2.3.3 ChEBI ID

2.3.4 DrugBank ID

2.3.5 DSSTox Substance ID

2.3.6 Metabolomics Workbench ID

2.3.7 NCI Thesaurus Code

2.3.8 PharmGKB ID

2.3.9 Wikidata

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Euthroid
  • Euthyral
  • liotrix
  • Thyreotom
  • Thyrolar
  • thyroxine - triiodothyronine combination
  • thyroxine - triiodothyronine combination, monosodium salt
  • thyroxine, triiodothyronine drug combination
  • triiodothyronine - thyroxine combination

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
1471.8 g/mol
Reference
Computed by PubChem 2.1 (PubChem release 2021.05.07)
Property Name
Hydrogen Bond Donor Count
Property Value
4
Reference
Computed by Cactvs 3.4.6.11 (PubChem release 2019.06.18)
Property Name
Hydrogen Bond Acceptor Count
Property Value
10
Reference
Computed by Cactvs 3.4.6.11 (PubChem release 2019.06.18)
Property Name
Rotatable Bond Count
Property Value
8
Reference
Computed by Cactvs 3.4.6.11 (PubChem release 2019.06.18)
Property Name
Exact Mass
Property Value
1471.4406 Da
Reference
Computed by PubChem 2.1 (PubChem release 2021.05.07)
Property Name
Monoisotopic Mass
Property Value
1471.4406 Da
Reference
Computed by PubChem 2.1 (PubChem release 2021.05.07)
Property Name
Topological Polar Surface Area
Property Value
191 Ų
Reference
Computed by Cactvs 3.4.6.11 (PubChem release 2019.06.18)
Property Name
Heavy Atom Count
Property Value
49
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
811
Reference
Computed by Cactvs 3.4.6.11 (PubChem release 2019.06.18)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
2
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
4
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2019.01.04)

3.2 Chemical Classes

3.2.1 Drugs

3.2.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Thyroid Hormones
Human drug -> Discontinued
Human drug -> Active ingredient (LIOTRIX)

5 Chemical Vendors

6 Drug and Medication Information

6.1 Drug Indication

May be used to treat primary, secondary or tertiary hypothyroidism. May also be used to suppress thyroid stimulating hormone (TSH) secretion in patients with simple (nontoxic) goiter, subacute or chronic lymphocytic thyroiditis multinodular goiter, and in the management of thyroid cancer. May be used in conjunction with other antithyroid agents to treat thyrotoxicosis to prevent goitrogenesis and hypothyroidism. May also be used for differential diagnosis of suspected mild hyperthyroidism or thyroid gland autonomy.

6.2 Drug Classes

Breast Feeding; Lactation; Milk, Human; Thyroid Hormones

6.3 FDA Approved Drugs

6.4 FDA Orange Book

7 Pharmacology and Biochemistry

7.1 Pharmacodynamics

Thyroid hormone drugs are natural or synthetic preparations containing T4 or T3 or both. T4 and T3 are produced in the human thyroid gland by the iodination and coupling of the amino acid tyrosine. Liotrix is a synthetic preparation of T4 and T3 in a 4:1 weight-based ratio. These hormones enhance oxygen consumption by most tissues of the body and increase the basal metabolic rate and the metabolism of carbohydrates, lipids and proteins. Thus, they exert a profound influence on every organ system in the body and are of particular importance in the development of the central nervous system.

7.2 Absorption, Distribution and Excretion

Route of Elimination
Thyroid hormones are primarily eliminated by the kidneys.

7.3 Mechanism of Action

The hormones, T4 and T3, are tyrosine-based hormones produced by the thyroid gland. Iodine is an important component in their synthesis. The major secreted form of thyroid hormone is T4. T4 is converted T3, the more active thyroid hormone, by deiodinases in peripheral tissues. T3 acts in the body to increase basal metabolic rate, alter protein synthesis and increase the body's sensitivity to catecholamines (such as adrenaline). Thyroid hormones are essential for proper development and differentiation of all cells of the human body. T4 and T3 regulate protein, fat and carbohydrate metabolism to varying extents. The most pronounced effect of the hormones is in altering how human cells use energetic compounds. The thyroid hormone derivatives bind to the thyroid hormone receptors initially to initiate their downstream effects.

8 Use and Manufacturing

8.1 Uses

8.1.1 Use Classification

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

9 Toxicity

9.1 Toxicological Information

9.1.1 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Liotrix is a mixture of levothyroxine (T4) and liothyronine (T3), which are normal components of human milk. Limited data on exogenous replacement doses of levothyroxine during breastfeeding indicate no adverse effects in infants. No information is available on the use of exogenous liothyronine during breastfeeding. The American Thyroid Association recommends that subclinical and overt hypothyroidism should be treated with levothyroxine in lactating women seeking to breastfeed. Thyroid dosage requirement may be increased in the postpartum period compared to prepregnancy requirements patients with Hashimoto's thyroiditis.

◉ Effects in Breastfed Infants

Effects of exogenous thyroid hormone administration to mothers on their infant have not been reported. One case of apparent mitigation of cretinism in hypothyroid infants by breastfeeding has been reported, but the amounts of thyroid hormones in milk are not optimal, and this result has been disputed. The thyroid hormone content of human milk from the mothers of very preterm infants appears not to be sufficient to affect the infants' thyroid status. The amounts of thyroid hormones in milk are apparently not sufficient to interfere with diagnosis of hypothyroidism.

In a telephone follow-up study, 5 nursing mothers reported taking levothyroxine (dosage unspecified). The mothers reported no adverse reactions in their infants.

One mother with who had undergone a thyroidectomy was taking levothyroxine 100 mcg daily as well as calcium carbonate and calcitriol. Her breastfed infant was reportedly "thriving" at 3 months of age.

◉ Effects on Lactation and Breastmilk

Adequate thyroid hormone serum levels are required for normal lactation. Replacing deficient thyroid levels should improve milk production caused by hypothyroidism. Supraphysiologic doses would not be expected to further improve lactation.

9.1.2 Acute Effects

10 Literature

10.1 Consolidated References

10.2 NLM Curated PubMed Citations

10.3 Springer Nature References

10.4 Chemical Co-Occurrences in Literature

10.5 Chemical-Gene Co-Occurrences in Literature

10.6 Chemical-Disease Co-Occurrences in Literature

11 Patents

11.1 Depositor-Supplied Patent Identifiers

11.2 WIPO PATENTSCOPE

11.3 Chemical Co-Occurrences in Patents

11.4 Chemical-Disease Co-Occurrences in Patents

11.5 Chemical-Gene Co-Occurrences in Patents

12 Interactions and Pathways

12.1 Chemical-Target Interactions

12.2 Drug-Drug Interactions

12.3 Drug-Food Interactions

  • Avoid calcium supplements/calcium rich foods. Calcium may interfere with the absorption of this drug by forming an insoluble complex. Separate medication administration by at least 4 hours.
  • Avoid grapefruit products. Grapefruit may delay the absorption of this medicaiton.
  • Avoid high-fiber foods. High-fiber foods may affect absorption. Separate medication administration by at least 1 hour.
  • Avoid iron supplements. Iron may interfere with the absorption of this drug by forming an insoluble complex. Separate medication administration by at least 4 hours.
  • Avoid multivalent ions. Avoid iron and calcium containing products as well as antacids.
  • Take before a meal. Take 30-60 minutes before breakfast.
  • Take on an empty stomach.

13 Classification

13.1 MeSH Tree

13.2 NCI Thesaurus Tree

13.3 ChEBI Ontology

13.4 ChemIDplus

13.5 EPA DSSTox Classification

13.6 MolGenie Organic Chemistry Ontology

14 Information Sources

  1. ChEBI
  2. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  3. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  4. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  5. Drugs and Lactation Database (LactMed)
  6. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  7. FDA Orange Book
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  8. Metabolomics Workbench
  9. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  10. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  11. Springer Nature
  12. Wikidata
  13. PubChem
  14. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
    thyroxine, triiodothyronine drug combination
    https://www.ncbi.nlm.nih.gov/mesh/67018539
  15. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  16. PATENTSCOPE (WIPO)
CONTENTS