Details of the Drug

General Information of Drug (ID: DM6IR3P)

Drug Name

Liothyronine

Synonyms

liothyronine; 3,3',5-Triiodo-L-thyronine; 6893/2/3; Liothyronin; Tresitope; 3,5,3'-triiodothyronine; L-Liothyronine; O-(4-Hydroxy-3-iodophenyl)-3,5-diiodo-L-tyrosine; triothyrone; Liothyroninum; Liotironina; 3,5,3'-Triiodo-L-thyronine; L-T3; T3; 3,3',5-Triiodothyronine; Triiodo-L-thyronine; Lyothyronine; 3,5,3'TRIIODOTHYRONINE; L-3,5,3'-Triiodothyronine; (2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoic acid; T3 (amino acid); T3 (Hormone); L-3,3',5-TriioDOThyronine; Liothyronine [INN:BAN]; Rathyronine; Triothyrone; THYROID HORMONE; Liothyronine I 131; Liothyronine I 131 [USAN]; T3 liothyronine; Cytomel (TN); Euthroid-1; Euthroid-2; Euthroid-3; Liothyronine (INN); Liothyroninum[INN-Latin]; Liotironina [INN-Spanish]; T3 (Triiodothyronine); T3 (VAN); Tertroxin (TN); Thyrolar-1; Thyrolar-2; Thyrolar-3; Tri-Thyrotope; Triiodothyronine (T3); Triomet-131; Euthroid-05; Thyrolar-025; Thyrolar-05; TRIIODOTHYRONINE (T3 OR LIOTHYRONINE, ACTIVE) (6-11%); Thyronine, 3,3',5-triiodo-, L-(6CI); L-3-(4-(4-Hydroxy-3-iodophenoxy)-3,5-diiodophenyl)alanine; L-Tyrosine, O-(4-hydroxy-3-iodophenyl)-3,5-diiodo-(9CI); 3,3'5-Triiodo-L-thyronine; 3,5,3'-Tri-iodo-L-thyronine; 4-(3-Iodo-4-hydroxyphenoxy)-3,5-diiodophenylalanine; 4-(4-Hydroxy-3-iodophenoxy)-3,5-diiodophenylalanine; 4-(4-hydroxy-3-iodophenoxy)-3,5-diiodo-L-phenylalanine

Indication

Disease Entry	ICD 11	Status	REF
Congenital hypothyroidism	N.A.	Approved	[1]
Edema	MG29	Approved	[1]
Goiter	N.A.	Approved	[1]
Hypothyroidism	5A00	Approved	[2]
Thyroid cancer	2D10	Approved	[1]
Congestive heart failure	BD10	Phase 3	[3]
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Therapeutic Class

Hormone Replacement Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

650.97

Logarithm of the Partition Coefficient (xlogp)

1.7

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [4]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.00257 micromolar/kg/day [5]

Chemical Identifiers

Formula: C15H12I3NO4
IUPAC Name: (2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoic acid
Canonical SMILES: C1=CC(=C(C=C1OC2=C(C=C(C=C2I)C[C@@H](C(=O)O)N)I)I)O
InChI: InChI=1S/C15H12I3NO4/c16-9-6-8(1-2-13(9)20)23-14-10(17)3-7(4-11(14)18)5-12(19)15(21)22/h1-4,6,12,20H,5,19H2,(H,21,22)/t12-/m0/s1
InChIKey: AUYYCJSJGJYCDS-LBPRGKRZSA-N

Cross-matching ID

PubChem CID: 5920
ChEBI ID: CHEBI:18258
CAS Number: 15785-49-6
DrugBank ID: DB00279
TTD ID: D0S6JG
VARIDT ID: DR00173
INTEDE ID: DR0959
ACDINA ID: D00368

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Thyroid hormone receptor alpha (THRA)	TTTSEPU	THA_HUMAN	Antagonist	[6]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 1C1 (SLCO1C1)	DTPYCQ4	SO1C1_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 4A1 (SLCO4A1)	DT8H2IC	SO4A1_HUMAN	Substrate	[8]
Organic anion transporting polypeptide 4C1 (SLCO4C1)	DTY0QMU	SO4C1_HUMAN	Substrate	[8]
Sodium/taurocholate cotransporting polypeptide (SLC10A1)	DT56EKP	NTCP_HUMAN	Substrate	[9]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[10]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[11]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[12]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Substrate	[13]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Substrate	[14]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1)	OTG2T749	CP24A_HUMAN	Gene/Protein Processing	[15]
A-kinase anchor protein 12 (AKAP12)	OTCVRDDX	AKA12_HUMAN	Gene/Protein Processing	[16]
Abnormal spindle-like microcephaly-associated protein (ASPM)	OTKXQMNA	ASPM_HUMAN	Gene/Protein Processing	[16]
Acyl-CoA-binding domain-containing protein 4 (ACBD4)	OTVR7MLK	ACBD4_HUMAN	Gene/Protein Processing	[16]
Akirin-2 (AKIRIN2)	OTQ6WSKW	AKIR2_HUMAN	Gene/Protein Processing	[16]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Protein Interaction/Cellular Processes	[17]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Gene/Protein Processing	[18]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Gene/Protein Processing	[18]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Gene/Protein Processing	[18]
All-trans-retinol dehydrogenase ADH1B (ADH1B)	OTV3TB81	ADH1B_HUMAN	Gene/Protein Processing	[18]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Liothyronine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Sucralfate	DMP9HBO	Minor	Decreased absorption of Liothyronine due to formation of complexes caused by Sucralfate.	Acne vulgaris [ED80]	[19]
Methylphenobarbital	DMDSWAG	Moderate	Increased metabolism of Liothyronine caused by Methylphenobarbital mediated induction of CYP450 enzyme.	Anxiety disorder [6B00-6B0Z]	[20]
Rabeprazole	DMMZXIW	Moderate	Decreased absorption of Liothyronine due to altered gastric pH caused by Rabeprazole.	Bacterial infection [1A00-1C4Z]	[21]
Esterified estrogens	DM9KZDO	Moderate	Decreased plasma concentration of Liothyronine caused by Esterified estrogens mediated increased concentration of serum thyroid-binding globulin.	Breast cancer [2C60-2C6Y]	[22]
Quinestrol	DMJ6H1Z	Moderate	Decreased plasma concentration of Liothyronine caused by Quinestrol mediated increased concentration of serum thyroid-binding globulin.	Breast cancer [2C60-2C6Y]	[22]
Estradiol	DMUNTE3	Moderate	Decreased plasma concentration of Liothyronine caused by Estradiol mediated increased concentration of serum thyroid-binding globulin.	Breast cancer [2C60-2C6Y]	[22]
Secobarbital	DM14RF5	Moderate	Increased metabolism of Liothyronine caused by Secobarbital mediated induction of CYP450 enzyme.	Chronic insomnia [7A00]	[20]
Anisindione	DM2C48U	Moderate	Increased risk of bleeding by the combination of Liothyronine and Anisindione.	Coagulation defect [3B10]	[23]
Mestranol	DMG3F94	Moderate	Decreased plasma concentration of Liothyronine caused by Mestranol mediated increased concentration of serum thyroid-binding globulin.	Contraceptive management [QA21]	[22]
[3H]estrone-3-sulphate	DMGPF0N	Moderate	Decreased plasma concentration of Liothyronine caused by [3H]estrone-3-sulphate mediated increased concentration of serum thyroid-binding globulin.	Discovery agent [N.A.]	[22]
Primidone	DM0WX6I	Moderate	Increased metabolism of Liothyronine caused by Primidone mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[20]
Phenobarbital	DMXZOCG	Moderate	Increased metabolism of Liothyronine caused by Phenobarbital mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[20]
Carbamazepine	DMZOLBI	Moderate	Increased plasma concentration of Liothyronine and Carbamazepine due to competitive binding of plasma proteins.	Epilepsy/seizure [8A61-8A6Z]	[20]
Dexlansoprazole	DM1DBV5	Moderate	Decreased absorption of Liothyronine due to altered gastric pH caused by Dexlansoprazole.	Gastro-oesophageal reflux disease [DA22]	[21]
Omeprazole	DM471KJ	Moderate	Decreased absorption of Liothyronine due to altered gastric pH caused by Omeprazole.	Gastro-oesophageal reflux disease [DA22]	[21]
Digoxin	DMQCTIH	Moderate	Increased renal excretion of Liothyronine caused by Digoxin.	Heart failure [BD10-BD1Z]	[24]
Digitoxin	DMWVIGP	Moderate	Increased renal excretion of Liothyronine caused by Digitoxin.	Heart failure [BD10-BD1Z]	[24]
Rifampin	DMA8J1G	Moderate	Increased metabolism of Liothyronine caused by Rifampin mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[21]
Rifapentine	DMCHV4I	Moderate	Increased metabolism of Liothyronine caused by Rifapentine mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[21]
Didanosine	DMI2QPE	Moderate	Decreased absorption of Liothyronine due to formation of complexes caused by Didanosine.	Human immunodeficiency virus disease [1C60-1C62]	[25]
Amobarbital	DM0GQ8N	Moderate	Increased metabolism of Liothyronine caused by Amobarbital mediated induction of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[20]
Pentobarbital	DMFNH7L	Moderate	Increased metabolism of Liothyronine caused by Pentobarbital mediated induction of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[20]
Iron	DMAP8MV	Moderate	Decreased absorption of Liothyronine due to formation of complexes caused by Iron.	Iron deficiency anaemia [3A00]	[25]
Dienestrol	DMBSXI0	Moderate	Decreased plasma concentration of Liothyronine caused by Dienestrol mediated increased concentration of serum thyroid-binding globulin.	Menopausal disorder [GA30]	[22]
Conjugated estrogens	DMLT0E1	Moderate	Decreased plasma concentration of Liothyronine caused by Conjugated estrogens mediated increased concentration of serum thyroid-binding globulin.	Menopausal disorder [GA30]	[22]
Ethinyl estradiol	DMODJ40	Moderate	Decreased plasma concentration of Liothyronine caused by Ethinyl estradiol mediated increased concentration of serum thyroid-binding globulin.	Menopausal disorder [GA30]	[22]
Rifabutin	DM1YBHK	Moderate	Increased metabolism of Liothyronine caused by Rifabutin mediated induction of CYP450 enzyme.	Mycobacterium infection [1B10-1B21]	[21]
Orlistat	DMRJSP8	Moderate	Decreased absorption of Liothyronine caused by Orlistat.	Obesity [5B80-5B81]	[26]
Esomeprazole	DM7BN0X	Moderate	Decreased absorption of Liothyronine due to altered gastric pH caused by Esomeprazole.	Peptic ulcer [DA61]	[21]
Estramustine	DMWTAOI	Moderate	Decreased plasma concentration of Liothyronine caused by Estramustine mediated increased concentration of serum thyroid-binding globulin.	Prostate cancer [2C82]	[22]
Warfarin	DMJYCVW	Moderate	Increased risk of bleeding by the combination of Liothyronine and Warfarin.	Supraventricular tachyarrhythmia [BC81]	[23]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Stearic acid	E00079	5281	Emulsifying agent; Solubilizing agent; Viscosity-controlling agent; lubricant
Calcium sulfate anhydrous	E00303	24497	Desiccant; Diluent
Calcium sulfate dihydrate	E00315	24928	Desiccant; Diluent
Edetate disodium	E00186	8759	Complexing agent
Gelatin	E00630	Not Available	Other agent
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Saccharose	E00091	5988	Binding agent; Coating agent; Cryoprotectant; Diluent; Flavoring agent; Suspending agent; Viscosity-controlling agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
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⏷ Show the Full List of 12 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Liothyronine 0.005 mg tablet	0.005 mg	Oral Tablet	Oral
Liothyronine 0.025 mg tablet	0.025 mg	Oral Tablet	Oral
Liothyronine 0.05 mg tablet	0.05 mg	Oral Tablet	Oral
Liothyronine Sodium 25ug tablet	25ug	Tablet	Oral
Liothyronine Sodium 100mg tablet	100mg	Tablet	Oral
Liothyronine Sodium 25mg tablet	25mg	Tablet	Oral
Liothyronine Sodium 5mg tablet	5mg	Tablet	Oral

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References

1	Liothyronine FDA Label
2	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3	ClinicalTrials.gov (NCT00790738) Liothyronine (T3) for Bipolar Depression. U.S. National Institutes of Health.
4	BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	Evaluation of thyroid hormone action in a case of generalized resistance to thyroid hormone with chronic thyroiditis: discovery of a novel heterozy... Endocr J. 2007 Dec;54(5):727-32.
7	Involvement of multispecific organic anion transporter, Oatp14 (Slc21a14), in the transport of thyroxine across the blood-brain barrier. Endocrinology. 2004 Sep;145(9):4384-91.
8	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.
9	Identification of thyroid hormone transporters. Biochem Biophys Res Commun. 1999 Jan 19;254(2):497-501.
10	Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12.
11	Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. J Biol Chem. 1999 Jun 11;274(24):17159-63.
12	LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99.
13	FDA Label of Liothyronine sodium. The 2020 official website of the U.S. Food and Drug Administration.
14	Characterization of human liver thermostable phenol sulfotransferase (SULT1A1) allozymes with 3,3',5-triiodothyronine as the substrate. J Endocrinol. 2001 Dec;171(3):525-32.
15	Similarities and differences between two modes of antagonism of the thyroid hormone receptor. ACS Chem Biol. 2011 Oct 21;6(10):1096-106.
16	Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
17	In vitro fluorescence displacement investigation of thyroxine transport disruption by bisphenol A. J Environ Sci (China). 2011;23(2):315-21. doi: 10.1016/s1001-0742(10)60408-1.
18	Thyroid hormone responsive genes in cultured human fibroblasts. J Clin Endocrinol Metab. 2005 Feb;90(2):936-43.
19	Havrankova J, Lahaie R "Levothyroxine binding by sucralfate." Ann Intern Med 117 (1992): 445-6. [PMID: 1503346]
20	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
21	Cerner Multum, Inc. "Australian Product Information.".
22	Arafah BM "Increased need for thyroxine in women with hypothyroidism during estrogen therapy." N Engl J Med 344 (2001): 1743-9. [PMID: 11396440]
23	Costigan DC, Freedman MH, Ehrlich RM "Potentiation of oral anticoagulant effect by l-thyroxine." Clin Pediatr (Phila) 23 (1984): 172-4. [PMID: 6697623]
24	Frye RL, Braunwald E "Studies on digitalis. III: The influence of triiodothyronine on digitalis requirements." Circulation 23 (1961): 376-82. [PMID: 13702336]
25	Campbell NR, Hasinoff BB, Stalts H, Rao B, Wong NC "Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism." Ann Intern Med 117 (1992): 1010-3. [PMID: 1443969]
26	Filippatos TD, Derdemezis CS, Gazi IF, Nakou ES, Mikhailidis DP, Elisaf MS "Orlistat-associated adverse effects and drug interactions: a critical review." Drug Saf 31 (2008): 53-65. [PMID: 18095746]