Details of the Drug

General Information of Drug (ID: DMHN027)

• Drug Name: Levothyroxine
• Synonyms: Eltroxin; Euthyrox; Forthyron; Laevothyroxinum; Laevoxin; Levolet; Levothroid; Levothyrox; Levothyroxin; Levoxyl; Oroxine; Synthroid; THX; Tetraiodothyronine; Thyratabs; Thyrax; Thyreoideum; Thyroxevan; Thyroxin; Thyroxinal; Levothyroxine sodium; Synthroid sodium; Thyroxine [BAN]; Thyroxine iodine; LT00440967; T4 levothyroxine; DL-Thyroxin; Eltroxin (TN); Euthyrox (TN); Eutirox (TN); Forthyron (TN); L-Thryoxin; L-Thyroxin; L-thyroxine; Laevothyroxinum (acid); Levaxin (TN); Levo-T; Levothyroxine (BAN); Levothyroxinum (acid); Levoxyl (TN); Synthroid (TN); T-3850; T4 (Hormone); Thyrax (TN); Thyrox (TN); Thyroxine (VAN); Thyroxine (l); L-thyroxine (TN); Levothyroxine Sodium (L-thyroxine); Levothroid (*Sodiumsalt*); Synthroid (*Sodium salt*); Thyroxine, L-(8CI); L-3,5,3',5'-Tetraiodothyronine; O-(4-Hydroxy-3,5-diiodophenyl)-3,5-diiodotyrosine; Beta-((3,5-Diiodo-4-hydroxyphenoxy)-3,5-diiodophenyl)alanine; O-(4-Hydroxy-3,5-diidophenyl)-3,5-diiodo-L-tyrosine; O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosine; (-)-Thyroxine; (125I)T4; (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid; 2-amino-3-[4-(4-hydroxy-3,5-diiodo-phenoxy)-3,5-diiodo-phenyl]-propanoic acid; 3,3',5,5"-Tetraiodo-L-thyronine; 3,3',5,5''-Tetraiodo-L-thyronine; 3,3',5,5'-Tetraiodo-L-thyronine; 3,5,3',5'-Tetraiodo-L-thyronine; 3,5,3',5'-Tetraiodothyronine; 3,5,3'5'-Tetraiodo-L-thyronine; 3-(4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl)alanine; 3-[4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]-L-alanine; 4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodo-L-phenylalanine

Indication

Disease Entry	ICD 11	Status	REF
Hypothyroidism	5A00	Approved	[1], [2]

• Therapeutic Class: Antithyroid Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 776.87
  Topological Polar Surface Area (xlogp); 2.4
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 5
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
  Elimination: Approximately 20% of T<sub>4 is eliminated in the stool [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 6 - 7 days (T4), and 1 - 2 days (T3) [5]
  Metabolism: The drug is metabolized via sequential deiodination [5]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.00644 micromolar/kg/day [6]
  Water Solubility: The ability of drug to dissolve in water is measured as 0.000585 mg/mL [3]
• Chemical Identifiers:
  Formula: C15H11I4NO4
  IUPAC Name: (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
  Canonical SMILES: C1=C(C=C(C(=C1I)OC2=CC(=C(C(=C2)I)O)I)I)C[C@@H](C(=O)O)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
  InChIKey: XUIIKFGFIJCVMT-LBPRGKRZSA-N
• Cross-matching ID:
  PubChem CID: 5819
  ChEBI ID: CHEBI:18332
  CAS Number: 51-48-9
  DrugBank ID: DB00451
  TTD ID: D06RGG
  VARIDT ID: DR00107
  INTEDE ID: DR0948

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	[7], [8]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 1C1 (SLCO1C1)	DTPYCQ4	SO1C1_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]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[12]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Substrate	[13]

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Glibenclamide	DM8JXPZ	Moderate	Antagonize the effect of Levothyroxine when combined with Glibenclamide.	Acute diabete complication [5A2Y]	[57]
Methylphenobarbital	DMDSWAG	Moderate	Increased metabolism of Levothyroxine caused by Methylphenobarbital mediated induction of CYP450 enzyme.	Anxiety disorder [6B00-6B0Z]	[58]
Rabeprazole	DMMZXIW	Moderate	Decreased absorption of Levothyroxine due to altered gastric pH caused by Rabeprazole.	Bacterial infection [1A00-1C4Z]	[59]
Esterified estrogens	DM9KZDO	Moderate	Decreased plasma concentration of Levothyroxine caused by Esterified estrogens mediated increased concentration of serum thyroid-binding globulin.	Breast cancer [2C60-2C6Y]	[60]
Quinestrol	DMJ6H1Z	Moderate	Decreased plasma concentration of Levothyroxine caused by Quinestrol mediated increased concentration of serum thyroid-binding globulin.	Breast cancer [2C60-2C6Y]	[60]
Estradiol	DMUNTE3	Moderate	Decreased plasma concentration of Levothyroxine caused by Estradiol mediated increased concentration of serum thyroid-binding globulin.	Breast cancer [2C60-2C6Y]	[60]
Anisindione	DM2C48U	Moderate	Increased risk of bleeding by the combination of Levothyroxine and Anisindione.	Coagulation defect [3B10]	[61]
Mestranol	DMG3F94	Moderate	Decreased plasma concentration of Levothyroxine caused by Mestranol mediated increased concentration of serum thyroid-binding globulin.	Contraceptive management [QA21]	[60]
[3H]estrone-3-sulphate	DMGPF0N	Moderate	Decreased plasma concentration of Levothyroxine caused by [3H]estrone-3-sulphate mediated increased concentration of serum thyroid-binding globulin.	Discovery agent [N.A.]	[60]
Primidone	DM0WX6I	Moderate	Increased metabolism of Levothyroxine caused by Primidone mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[58]
Phenobarbital	DMXZOCG	Moderate	Increased metabolism of Levothyroxine caused by Phenobarbital mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[58]
Carbamazepine	DMZOLBI	Moderate	Increased metabolism of Levothyroxine caused by Carbamazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[58]
Dexlansoprazole	DM1DBV5	Moderate	Decreased absorption of Levothyroxine due to altered gastric pH caused by Dexlansoprazole.	Gastro-oesophageal reflux disease [DA22]	[59]
Rifampin	DMA8J1G	Moderate	Increased metabolism of Levothyroxine caused by Rifampin mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[59]
Rifapentine	DMCHV4I	Moderate	Increased metabolism of Levothyroxine caused by Rifapentine mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[59]
Didanosine	DMI2QPE	Moderate	Decreased absorption of Levothyroxine due to formation of complexes caused by Didanosine.	Human immunodeficiency virus disease [1C60-1C62]	[62]
Ritonavir	DMU764S	Moderate	Increased metabolism of Levothyroxine caused by Ritonavir mediated induction of UGT.	Human immunodeficiency virus disease [1C60-1C62]	[63]
Quinapril	DMR8H31	Moderate	Decreased absorption of Levothyroxine due to formation of complexes caused by Quinapril.	Hypertension [BA00-BA04]	[58]
Amobarbital	DM0GQ8N	Moderate	Increased metabolism of Levothyroxine caused by Amobarbital mediated induction of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[58]
Iron	DMAP8MV	Moderate	Decreased absorption of Levothyroxine due to formation of complexes caused by Iron.	Iron deficiency anaemia [3A00]	[62]
Linaclotide	DM4EGV0	Moderate	Altered absorption of Levothyroxine caused by Linaclotide.	Irritable bowel syndrome [DD91]	[58]
Estrone	DM5T6US	Moderate	Decreased plasma concentration of Levothyroxine caused by Estrone mediated increased concentration of serum thyroid-binding globulin.	Menopausal disorder [GA30]	[60]
Dienestrol	DMBSXI0	Moderate	Decreased plasma concentration of Levothyroxine caused by Dienestrol mediated increased concentration of serum thyroid-binding globulin.	Menopausal disorder [GA30]	[60]
Ethinyl estradiol	DMODJ40	Moderate	Decreased plasma concentration of Levothyroxine caused by Ethinyl estradiol mediated increased concentration of serum thyroid-binding globulin.	Menopausal disorder [GA30]	[60]
Lanthanum carbonate	DMMJQSH	Moderate	Decreased absorption of Levothyroxine due to formation of complexes caused by Lanthanum carbonate.	Mineral absorption/transport disorder [5C64]	[58]
Rifabutin	DM1YBHK	Moderate	Increased metabolism of Levothyroxine caused by Rifabutin mediated induction of CYP450 enzyme.	Mycobacterium infection [1B10-1B21]	[59]
Orlistat	DMRJSP8	Moderate	Decreased absorption of Levothyroxine caused by Orlistat.	Obesity [5B80-5B81]	[64]
Esomeprazole	DM7BN0X	Moderate	Decreased absorption of Levothyroxine due to altered gastric pH caused by Esomeprazole.	Peptic ulcer [DA61]	[59]
Estramustine	DMWTAOI	Moderate	Decreased plasma concentration of Levothyroxine caused by Estramustine mediated increased concentration of serum thyroid-binding globulin.	Prostate cancer [2C82]	[60]
Warfarin	DMJYCVW	Moderate	Increased risk of bleeding by the combination of Levothyroxine and Warfarin.	Supraventricular tachyarrhythmia [BC81]	[61]

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