Details of the Drug

General Information of Drug (ID: DMDEXQ0)

Drug Name

Febuxostat

Synonyms

Adenuric; TEI; Uloric; Febuxostat [USAN]; S1547; TMX 67; Tei 6720; TMX-67; Tei-6720; Uloric (TN); Febuxostat (JAN/USAN/INN); TMX-67, Adenuric, Uloric, Febuxostat; 111GE013; 2-(3-CYANO-4-ISOBUTOXY-PHENYL)-4-METHYL-5-THIAZOLE-CARBOXYLIC ACID; 2-(3-Cyano-4-(2-methylpropoxy)phenyl)-4-methylthiazole-5-carboxylic acid;2-(3-Cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid; 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Hyperuricaemia	5C55.Y	Approved	[1], [2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

316.4

Topological Polar Surface Area (xlogp)

3.9

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 1.6 +/- 0.6 mg/L [3]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1-1.5 h [3]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [4]
Clearance: The total clearance of drug is 10-12 L/h [3]
Elimination: Following oral administration of 80 mg radiolabeled febuxostat, approximately 49% of the dose was recovered in the urine [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 5 - 8 hours [5]
Metabolism: The drug is metabolized via the liver [5]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 3.61228 micromolar/kg/day [6]
Vd: The volume of distribution (Vd) of drug is 29-75 L [7]
Water Solubility: The ability of drug to dissolve in water is measured as 0.013 mg/mL [4]

Chemical Identifiers

Formula: C16H16N2O3S
IUPAC Name: 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid
Canonical SMILES: CC1=C(SC(=N1)C2=CC(=C(C=C2)OCC(C)C)C#N)C(=O)O
InChI: InChI=1S/C16H16N2O3S/c1-9(2)8-21-13-5-4-11(6-12(13)7-17)15-18-10(3)14(22-15)16(19)20/h4-6,9H,8H2,1-3H3,(H,19,20)
InChIKey: BQSJTQLCZDPROO-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 134018
ChEBI ID: CHEBI:31596
CAS Number: 144060-53-7
DrugBank ID: DB04854
TTD ID: D0A5SE
INTEDE ID: DR0681
ACDINA ID: D00265

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Xanthine dehydrogenase/oxidase (XDH)	TT7RJY8	XDH_HUMAN	Inhibitor	[8], [2]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)_{Main DME}	DEYGVN4	UD11_HUMAN	Substrate	[9]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Febuxostat and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[29]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Febuxostat and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[30]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Febuxostat and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[31]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Febuxostat and Cannabidiol.	Epileptic encephalopathy [8A62]	[32]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Febuxostat and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[33]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Febuxostat and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[34]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Febuxostat and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[35]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Febuxostat and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[36]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Febuxostat and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[37]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Febuxostat and Idelalisib.	Mature B-cell leukaemia [2A82]	[38]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Febuxostat and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[32]
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⏷ Show the Full List of 11 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Carmellose sodium	E00625	Not Available	Disintegrant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Febuxostat 40 mg tablet	40 mg	Oral Tablet	Oral
Febuxostat 80 mg tablet	80 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6817).
2	Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
3	Hu M, Tomlinson B: Febuxostat in the management of hyperuricemia and chronic gout: a review. Ther Clin Risk Manag. 2008 Dec;4(6):1209-20. doi: 10.2147/tcrm.s3310.
4	BDDCS applied to over 900 drugs
5	FDA Approved Products: Uloric (febuxostat) oral tablets
6	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
7	Grabowski BA, Khosravan R, Vernillet L, Mulford DJ: Metabolism and excretion of [14C] febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, in healthy male subjects. J Clin Pharmacol. 2011 Feb;51(2):189-201. doi: 10.1177/0091270010365549. Epub 2010 Mar 30.
8	Clinical pipeline report, company report or official report of Takeda (2009).
9	In vitro drug-drug interaction studies with febuxostat, a novel non-purine selective inhibitor of xanthine oxidase: plasma protein binding, identification of metabolic enzymes and cytochrome P450 inhibition. Xenobiotica. 2008 May;38(5):496-510.
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12	Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen. Dose Response. 2017 Sep 11;15(3):1559325817723731.
13	UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80.
14	Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
15	Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
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19	Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.
20	Allopurinol: xanthine oxidase inhibitor. Tex Med. 1966 Jan;62(1):100-1.
21	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
22	Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin. J Nat Prod. 2009 Apr;72(4):725-31.
23	Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of superoxide radical. Biochem Pharmacol. 1988 Jan 15;37(2):349-52.
24	Inhibition of cow's milk xanthine oxidase by flavonoids. J Nat Prod. 1988 Mar-Apr;51(2):345-8.
25	QT/QTc study conducted in Japanese adult healthy subjects: a novel xanthine oxidase inhibitor topiroxostat was not associated with QT prolongation. J Clin Pharmacol. 2014 Apr;54(4):446-52.
26	Clinical pipeline report, company report or official report of Teijin Pharma.
27	Pharmacokinetics, pharmacodynamics, and tolerability of LC350189, a novel xanthine oxidase inhibitor, in healthy subjects. Drug Des Devel Ther. 2015 Aug 31;9:5033-49.
28	An updated patent review: xanthine oxidase inhibitors for the treatment of hyperuricemia and gout (2011-2015).Expert Opin Ther Pat. 2017 Mar;27(3):311-345.
29	Cerner Multum, Inc. "Australian Product Information.".
30	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
31	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
32	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
33	Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
34	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
35	Canadian Pharmacists Association.
36	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
37	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
38	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.