Drug/Small Molecule:
levothyroxine

2D structure

Overview

Generic Names: (-)-Thyroxine; 3,3',5,5'-Tetraiodo-L-thyronine; L-Thryoxin; L-Thyroxine; Laevothyroxinum; Levo-t; Levothyroxin; Levothyroxine Sodium; O-(4-Hydroxy-3,5-diidophenyl)-3,5-diiodo-L-tyrosine; T4 levothyroxine; THX; Tetraiodothyronine; Thyroxine iodine
IUPAC Name: (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
Trade Names: Eltroxin; Euthyrox; Laevoxin; Letter; Levaxin; Levolet; Levothroid; Levothyrox; Levoxine; Levoxyl; Novothyrox; Oroxine; Synthroid; Synthroid Sodium; Thyratabs; Thyrax; Thyreoideum; Thyro-tabs; Thyroxevan; Thyroxin; Thyroxinal; Unithroid
Brand Mixtures: Liotrix (Levothyroxine + Liothyronine); Thyrolar (Levothyroxine + Liothyronine)
PharmGKB Accession Id: PA450221

Description

The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. [PubChem]

Indication

For use alone or in combination with antithyroid agents to treat hypothyroidism, goiter, chronic lymphocytic thyroiditis, myxedema coma, and stupor.

ATC Therapeutic Category

  • H03AA:Thyroid hormones

Pharmacology and Interactions

Mechanism Of Action

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.

Pharmacology

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 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.

Food Interactions

Consistent administration in relation to meals is recommended. No iron within 4 hours of taking this medication. Take 30-60 minutes before breakfast.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic (primarily via cytochrome P450 isozyme 3A4).

Protein Binding

> 99%

Absorption

Bioavailability varies from 48% to 80%. Human studies have confirmed the importance of an intact jejunum and ileum for levothyroxine absorption and have shown some absorption from the duodenum.

Half Life

6 to 7 days

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.

Chemical Properties

Chemical Formula:

C15H11I4NO4

SMILES Code:

C1=C(C=C(C(=C1I)OC2=CC(=C(C(=C2)I)O)I)I)C[C@@H](C(=O)O)N

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

776.87 / 776.6867

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Metabolizing Enzymes

Drug Targets

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

acenocoumarol Thyroid hormones increase the anticoagulant effect
anisindione Thyroid hormones increase the anticoagulant effect
calcium Calcium decreases absorption of levothyroxine
cholestyramine The resin decreases the absorption of thyroid hormones
colestipol The resin decreases the absorption of thyroid hormones
dicumarol Thyroid hormones increase the anticoagulant effect
digoxin The thyroid hormone decreases the effect of digoxin
iron Iron decreases absorption of levothyroxine
raloxifene Raloxifene decreases absorption of levothyroxine
sucralfate Sucralfate decreases the effect of levothyroxine
warfarin Thyroid hormones increase the anticoagulant effect

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00451
ChEBI ID:
18332
KEGG Compound ID:
C01829
PubChem Compound ID:
5819
PubChem Substance ID:
7854286

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
The PharmGKB is financially supported by the NIH/ NIGMS and is managed at Stanford University (U01GM61374).
©2001-2010 PharmGKB.