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
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 (source: Drug Bank)

Indication

For use alone or in combination with antithyroid agents to treat hypothyroidism, goiter, chronic lymphocytic thyroiditis, myxedema coma, and stupor. (source: Drug Bank)

ATC Therapeutic Category

  • H03AA:Thyroid hormones

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Levothyroxine acts like the endogenous thyroid hormone thyroxine (T<sub>4</sub>, a tetra-iodinated tyrosine derivative). In the liver and kidney, T<sub>4</sub> is converted to T<sub>3</sub>, 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. (source: Drug Bank)

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. (source: Drug Bank)

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. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic (primarily via cytochrome P450 isozyme 3A4). (source: Drug Bank)

Protein Binding

> 99% (source: Drug Bank)

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. (source: Drug Bank)

Toxicity

LD<sub>50</sub>=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. (source: Drug Bank)

Isomeric SMILES Code:

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

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ABCB1
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No phenotype data No genotype data Literature annotations available Not annotated
CGA
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Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
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No phenotype data No genotype data Literature annotations available Not annotated
DIO1
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No phenotype data No genotype data Literature annotations available Not annotated
DIO2
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No phenotype data No genotype data Literature annotations available Not annotated
DIO3
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Phenotype data available Genotype Data Available Literature annotations available Has annotations
SULT1A1
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No phenotype data No genotype data Literature annotations available Not annotated
THRA
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No phenotype data No genotype data Literature annotations available Not annotated
THRB
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No phenotype data No genotype data Literature annotations available Not annotated
TRH
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No phenotype data No genotype data Literature annotations available Not annotated
TRHR
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No phenotype data No genotype data Literature annotations available Not annotated
TSHB
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Phenotype data available Genotype Data Available Literature annotations available Has annotations
UGT1A1
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Phenotype data available Genotype Data Available Literature annotations available Not annotated
UGT1A9
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No phenotype data No genotype data Literature annotations available Not annotated
UGT2B@
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Publications

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

Drug Targets

Gene Description
ALB Uncurated Annotation (source: Drug Bank)
CRYM Uncurated Annotation (source: Drug Bank)
SERPINA7 Uncurated Annotation (source: Drug Bank)
THRA Uncurated Annotation (source: Drug Bank)
THRB Uncurated Annotation (source: Drug Bank)
TTR Uncurated Annotation (source: Drug Bank)

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

Drug Interactions

Drug Description
acenocoumarol Uncurated Annotation Thyroid hormones increase the anticoagulant effect (source: Drug Bank)
calcium Uncurated Annotation Calcium decreases absorption of levothyroxine (source: Drug Bank)
cholestyramine Uncurated Annotation The resin decreases the absorption of thyroid hormones (source: Drug Bank)
colestipol Uncurated Annotation The resin decreases the absorption of thyroid hormones (source: Drug Bank)
dicumarol Uncurated Annotation Thyroid hormones increase the anticoagulant effect (source: Drug Bank)
digoxin Uncurated Annotation The thyroid hormone decreases the effect of digoxin (source: Drug Bank)
iron Uncurated Annotation Iron decreases absorption of levothyroxine (source: Drug Bank)
raloxifene Uncurated Annotation Raloxifene decreases absorption of levothyroxine (source: Drug Bank)
sucralfate Uncurated Annotation Sucralfate decreases the effect of levothyroxine (source: Drug Bank)
warfarin Uncurated Annotation Thyroid hormones increase the anticoagulant effect (source: Drug Bank)

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

Common Searches

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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.
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