Febuxostat

Identification

Summary

Febuxostat is a xanthine oxidase inhibitor used for the management of chronic hyperuricemia in adults with gout who have an inadequate response or intolerance to allopurinol.

Brand Names
Adenuric, Uloric
Generic Name
Febuxostat
DrugBank Accession Number
DB04854
Background

Febuxostat is a non-purine xanthine oxidase (XO) inhibitor.4 In early 2008, febuxostat was granted marketing authorization by the European Commission for the treatment of chronic hyperuricemia and gout.5 In the following year, the FDA for approved febuxostat for use in the chronic management of hyperuricemia in adult patients with gout who have an inadequate response or intolerance to allopurinol.10 Gout is a form of arthritis that is caused by the accumulation of uric acid crystal in or around a joint, leading to inflammation and further deposition of uric acid crystal deposition in bones, joints, tissues, and other organs in the long term. Gout is closely associated with hyperuricemia. Febuxostat works by inhibiting the activity of an enzyme that is responsible for the synthesis of uric acid, thereby reducing serum uric acid levels.5

In February 2019, a black box warning for febuxostat was added, based on the findings of a post-market clinical study (the CARES trial) where there was an increased risk of cardiovascular (CV) fatal outcomes in patients with gout and known cardiovascular disease treated with febuxostat, when compared to those treated with allopurinol. The manufacturer and the FDA advise health professionals to limit the use of febuxostat to second-line therapy in patients who have inadequate response or intolerance to allopurinol, and to avoid the use of febuxostat in patients with cardiovascular diseases.1,9

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 316.375
Monoisotopic: 316.088163078
Chemical Formula
C16H16N2O3S
Synonyms
  • 2-(3-cyano-4-isobutoxyphenyl)-4-methyl- 1,3-thiazole-5-carboxylic acid
  • Fébuxostat
  • Febuxostat
  • Febuxostatum
External IDs
  • TEI-6720
  • TMX-67

Pharmacology

Indication

Febuxostat is indicated for the chronic management of hyperuricemia in adult patients with gout who have an inadequate response to a maximally titrated dose of allopurinol, who are intolerant to allopurinol, or for whom treatment with allopurinol is not advisable. It is not recommended for the treatment of asymptomatic hyperuricemia 10 or secondary hyperuricemia.7

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Febuxostat is a novel, selective xanthine oxidase/dehydrogenase inhibitor that works by decreasing serum uric acid in a dose-dependent manner. In healthy subjects, febuxostat decreased the mean serum uric acid and serum xanthine concentrations, as well as the total urinary uric acid excretion. Febuxostat at daily doses of 40-80 mg reduced the 24-hour mean serum uric acid concentrations by 40 to 55%.10 Closely related to the drug-induced reduction of serum uric acid levels and mobilization of urate crystals in tissue deposits, febuxostat is associated with gout flares.7

Unlike allopurinol and oxypurinol, febuxostat has no inhibitory actions against other enzymes involved in purine and pyrimidine synthesis and metabolism, because it does not structurally resemble purines or pyrimidines.5

Mechanism of action

Gout is a form of acute arthritis that is characterized by the accumulation of crystals of monosodium urate and urate crystals in or around a joint, leading to inflammation and persistent urate crystal deposition in bones, joints, tissues, and other organs that may exacerbate over time. Hyperuricemia is closely related to gout, whereby it may exist for many years before the first clinical attack of gout; thus, aberrated serum uric acid levels and hyperuricemia are believed to be the biochemical aberration involved in the pathogenesis of gout.5 Xanthine oxidoreductase (XOR) can act as a xanthine oxidase or xanthine dehydrogenase. In humans, it is a critical enzyme for uric acid production as it catalyzes the oxidation reaction steps from hypoxanthine to xanthine and from xanthine to uric acid in the pathway of purine metabolism.6 Febuxostat potently inhibits XOR, blocking both its oxidase and dehydrogenase activities. With high affinity, febuxostat binds to XOR in a molecular channel leading to the molybdenum-pterin active site, where allopurinol demonstrates relatively weak competitive inhibition.5

XOR is mainly found in the dehydrogenase form under normal physiological conditions; however, in inflammatory conditions, XOR can be converted into the xanthine oxidase form, which catalyzes reactions that produce reactive oxygen species (ROS), such as peroxynitrite. ROS contribute to vascular inflammation and alterations in vascular function. As febuxostat can inhibit both forms of XOR, it can inhibit ROS formation, oxidative stress, and inflammation.2 In a rat model, febuxostat suppressed renal ischemia-reperfusion injury by attenuating oxidative stress.3

TargetActionsOrganism
AXanthine dehydrogenase/oxidase
inhibitor
Humans
Absorption

After oral administration, about 85% of febuxostat is absorbed rapidly.5 Tmax ranges from 1 to 1.5 hours. Following once-daily oral administration, Cmax was approximately 1.6 ± 0.6 mcg/mL at a dose of 40 mg febuxostat and 2.6 ± 1.7 mcg/mL at a dose of 80 mg febuxostat.10

A high-fat meal decreased Cmax by 49% and AUC by 18%, but there were no clinically significant changes in the ability of febuxostat to decrease serum uric acid concentrations.10

Volume of distribution

The apparent steady-state volume of distribution (Vss/F) of febuxostat ranges from 29 to 75 L, indicating a low to medium volume of distribution.8

Protein binding

Febuxostat is approximately 99.2% bound to plasma proteins, primarily to albumin. Plasma protein binding is constant over the concentration range achieved with 40 mg and 80 mg doses.10

Metabolism

Febuxostat is metabolized in the liver by UDP-glucuronosyltransferase (UGT) and Cytochrome P450 (CYP) enzymes, with the relative contribution of each enzyme isoform in the metabolism of febuxostat not fully elucidated. UGT1A1, UGT1A3, UGT1A9, and UGT2B7 mediate conjugation of febuxostat,10 which approximately accounts for 22–44% of the metabolism of the total dose administered, to produce the acyl-glucuronide metabolite.5 CYP1A2, CYP2C8, CYP2C9, and non-P450 enzymes are responsible for the oxidation reaction, which accounts for 2-8% of the metabolism of the dose.5 Oxidation reaction produces 67M-1, 67M-2, and 67M-4, which are pharmacologically active metabolites. 67M-1, 67M-2, and 67M-4 can further undergo glucuronidation and sulfation.8 Hydroxy metabolites are present in human plasma at much lower concentrations than the parent drug.10

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Route of elimination

Febuxostat is eliminated via both hepatic and renal pathways. Following oral administration of 80 mg radiolabeled febuxostat, approximately 49% of the dose was recovered in the urine. In urine, about 3% of the recovered dose accounted for unchanged febuxostat, 30% accounted for the acyl glucuronide metabolite, 13% accounted for oxidative metabolites and their conjugates, and 3% accounted for unidentified metabolites.10

Approximately 45% of the total dose was recovered in the feces, where 12% of the dose accounted for the unchanged parent drug. About 1% accounted for the acyl glucuronide metabolite, 25% accounted for oxidative metabolites and their conjugates, and 7% accounted for unidentified metabolites.10

Half-life

The apparent mean terminal elimination half-life of approximately 5 to 8 hours.10

Clearance

Following oral administration of single doses of 10 to 240 mg, the mean apparent total clearance ranged from 10 to 12 L/h.5

Adverse Effects
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Toxicity

Oral lowest published toxic dose (TDLO) in humans is 1.82 mg/kg/14D (intermittent).9 Oral LD50 is 300 mg/kg in mice, 3200 mg/kg in rabbits, and 980 mg/kg in rats.12

No dose-limiting toxicities were observed with febuxostat administered at doses up to 300 mg daily for seven days in healthy subjects. There are no reports of overdose of febuxostat in clinical studies and there is no known antidote. Overdose should be managed by symptomatic and supportive care.10

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbemaciclibThe excretion of Abemaciclib can be decreased when combined with Febuxostat.
AdenineThe metabolism of Febuxostat can be decreased when combined with Adenine.
AfatinibThe excretion of Afatinib can be decreased when combined with Febuxostat.
AllopurinolThe excretion of Allopurinol can be decreased when combined with Febuxostat.
AlpelisibThe serum concentration of Alpelisib can be increased when it is combined with Febuxostat.
AminophyllineThe serum concentration of the active metabolites of Aminophylline can be increased when Aminophylline is used in combination with Febuxostat.
AmitriptylineThe metabolism of Febuxostat can be decreased when combined with Amitriptyline.
ApixabanThe excretion of Apixaban can be decreased when combined with Febuxostat.
AtazanavirThe metabolism of Febuxostat can be decreased when combined with Atazanavir.
AzathioprineThe metabolism of Azathioprine can be decreased when combined with Febuxostat.
Interactions
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Food Interactions
  • Take with or without food. A high fat meal decreases Cmax and AUC in a clinically insignificant way.

Products

Products
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Product Images
International/Other Brands
Atenurix (Ajanta Pharma Phil) / Barif (Square) / Feburic (Teijin Pharma)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AdenuricTablet, film coated80 mgOralMenarini International Operations Luxembourg S.A. (Miol)2016-09-07Not applicableEU flag
AdenuricTablet, film coated80 mgOralMenarini International Operations Luxembourg S.A. (Miol)2016-09-07Not applicableEU flag
AdenuricTablet, film coated80 mgOralMenarini International Operations Luxembourg S.A. (Miol)2016-09-07Not applicableEU flag
AdenuricTablet, film coated120 mgOralMenarini International Operations Luxembourg S.A. (Miol)2016-09-07Not applicableEU flag
AdenuricTablet, film coated120 mgOralMenarini International Operations Luxembourg S.A. (Miol)2016-09-07Not applicableEU flag
AdenuricTablet, film coated120 mgOralMenarini International Operations Luxembourg S.A. (Miol)2016-09-07Not applicableEU flag
AdenuricTablet, film coated80 mgOralMenarini International Operations Luxembourg S.A. (Miol)2016-09-07Not applicableEU flag
AdenuricTablet, film coated80 mgOralMenarini International Operations Luxembourg S.A. (Miol)2016-09-07Not applicableEU flag
AdenuricTablet, film coated120 mgOralMenarini International Operations Luxembourg S.A. (Miol)2016-09-07Not applicableEU flag
AdenuricTablet, film coated80 mgOralMenarini International Operations Luxembourg S.A. (Miol)2016-09-07Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FebuxostatTablet40 mg/1OralTris Pharma Inc2020-09-28Not applicableUS flag
FebuxostatTablet80 mg/1OralGolden State Medical Supply Inc.2019-10-15Not applicableUS flag
FebuxostatTablet, film coated40 mg/1OralMylan Pharmaceuticals Inc.2019-07-01Not applicableUS flag
FebuxostatTablet80 mg/1OralSunshine Lake Pharma Co., Ltd.2020-06-02Not applicableUS flag
FebuxostatTablet, film coated40 mg/1OralAphena Pharma Solutions - Tennessee, LLC2019-12-30Not applicableUS flag
FebuxostatTablet40 mg/1OralHikma Pharmaceuticals USA Inc2019-11-11Not applicableUS flag
FebuxostatTablet, film coated80 mg/1OralNorthstar RxLLC2021-01-26Not applicableUS flag
FebuxostatTablet, coated80 mg/1OralAlembic Pharmaceuticals Limited2019-07-01Not applicableUS flag
FebuxostatTablet40 mg/1OralDr Reddy's Laboratories Limited2020-11-25Not applicableUS flag
FebuxostatTablet, film coated80 mg/1OralNovadoz Pharmaceuticals Llc2019-12-30Not applicableUS flag

Categories

ATC Codes
M04AA03 — Febuxostat
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as thiazolecarboxylic acids and derivatives. These are heterocyclic compounds containing a thiazole ring which bears a carboxylic acid group (or a derivative thereof).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Thiazoles
Direct Parent
Thiazolecarboxylic acids and derivatives
Alternative Parents
Phenoxy compounds / Phenol ethers / Benzonitriles / 2,4,5-trisubstituted thiazoles / Alkyl aryl ethers / Heteroaromatic compounds / Nitriles / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds
show 3 more
Substituents
2,4,5-trisubstituted 1,3-thiazole / Alkyl aryl ether / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Benzonitrile / Carbonitrile / Carboxylic acid / Carboxylic acid derivative / Ether
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
nitrile, 1,3-thiazolemonocarboxylic acid (CHEBI:45943)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
101V0R1N2E
CAS number
144060-53-7
InChI Key
BQSJTQLCZDPROO-UHFFFAOYSA-N
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)
IUPAC Name
2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid
SMILES
CC(C)COC1=C(C=C(C=C1)C1=NC(C)=C(S1)C(O)=O)C#N

References

Synthesis Reference

EPO Patent Report

General References
  1. Gandhi PK, Gentry WM, Bottorff MB: Cardiovascular thromboembolic events associated with febuxostat: investigation of cases from the FDA adverse event reporting system database. Semin Arthritis Rheum. 2013 Jun;42(6):562-6. doi: 10.1016/j.semarthrit.2012.11.002. Epub 2013 Jan 24. [Article]
  2. Saban-Ruiz J, Alonso-Pacho A, Fabregate-Fuente M, de la Puerta Gonzalez-Quevedo C: Xanthine oxidase inhibitor febuxostat as a novel agent postulated to act against vascular inflammation. Antiinflamm Antiallergy Agents Med Chem. 2013;12(1):94-9. [Article]
  3. Tsuda H, Kawada N, Kaimori JY, Kitamura H, Moriyama T, Rakugi H, Takahara S, Isaka Y: Febuxostat suppressed renal ischemia-reperfusion injury via reduced oxidative stress. Biochem Biophys Res Commun. 2012 Oct 19;427(2):266-72. doi: 10.1016/j.bbrc.2012.09.032. Epub 2012 Sep 17. [Article]
  4. Edwards NL: Febuxostat: a new treatment for hyperuricaemia in gout. Rheumatology (Oxford). 2009 May;48 Suppl 2:ii15-ii19. doi: 10.1093/rheumatology/kep088. [Article]
  5. 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. [Article]
  6. Nishino T, Okamoto K: Mechanistic insights into xanthine oxidoreductase from development studies of candidate drugs to treat hyperuricemia and gout. J Biol Inorg Chem. 2015 Mar;20(2):195-207. doi: 10.1007/s00775-014-1210-x. Epub 2014 Dec 12. [Article]
  7. Gerriets V, Jialal I: Febuxostat . [Article]
  8. 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. [Article]
  9. Takeda: Important Safety Information on ULORIC (febuxostat) – Increased Risk of Cardiovascular Fatal Outcomes [Link]
  10. FDA Approved Products: Uloric (febuxostat) oral tablets [Link]
  11. Selleck Chemicals: Febuxostat Safety Data Sheet [Link]
  12. : Clearsynth Labs: Febuxostat D9 Safety Data Sheet [Link]
KEGG Drug
D01206
PubChem Compound
134018
PubChem Substance
310264854
ChemSpider
118173
BindingDB
50320491
RxNav
73689
ChEBI
31596
ChEMBL
CHEMBL1164729
ZINC
ZINC000000005423
PharmGKB
PA165958521
PDBe Ligand
TEI
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Febuxostat
AHFS Codes
  • 92:16.00 — Antigout Agents
PDB Entries
1n5x
FDA label
Download (115 KB)
MSDS
Download (568 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic ScienceHigh Blood Pressure (Hypertension)1
4CompletedDiagnosticGouty Arthritis1
4CompletedTreatment24 Hour Blood Pressure / Gouty Arthritis / High Blood Pressure (Hypertension) / Prehypertension / Pulse Wave Velocity1
4CompletedTreatmentAdenine Phosphoribosyltransferase Deficiency1
4CompletedTreatmentChronic Kidney Disease (CKD) / Gouty Arthritis1
4CompletedTreatmentCoronary Artery Disease (CAD)1
4CompletedTreatmentGouty Arthritis2
4CompletedTreatmentHyperuricemia1
4CompletedTreatmentPrimary Gout1
4CompletedTreatmentType 1 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, film coatedOral120 MG
Tablet, coatedOral
Tablet, coatedOral40 mg
TabletOral
Tablet, film coatedOral
Tablet, coatedOral40 mg/1
Tablet, coatedOral80 mg/1
Tablet, film coatedOral40 mg/1
Tablet, film coatedOral80 mg/1
Tablet, coatedOral120 mg
Capsule, liquid filledOral120 mg
Capsule, liquid filledOral40 mg
Capsule, liquid filledOral80 mg
TabletOral40 mg/1
TabletOral80 mg
TabletOral80 mg/1
Tablet, coatedOral80 mg
Tablet, film coatedOral80 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5614520No1997-03-252019-03-25US flag
US8372872No2013-02-122031-09-08US flag
US9107912No2015-08-182031-09-08US flag
US6225474No2001-05-012019-06-18US flag
US7361676No2008-04-222024-03-08US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)238-239°Patent WO2012056442 A1
water solubility<1 mg/mLSelleck Chemicals Safety Data Sheet
Predicted Properties
PropertyValueSource
Water Solubility0.0183 mg/mLALOGPS
logP3.8ALOGPS
logP3.52ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)3.08ChemAxon
pKa (Strongest Basic)0.39ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area83.21 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity93.93 m3·mol-1ChemAxon
Polarizability33.88 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9865
Blood Brain Barrier+0.7853
Caco-2 permeable+0.5126
P-glycoprotein substrateNon-substrate0.7834
P-glycoprotein inhibitor INon-inhibitor0.8351
P-glycoprotein inhibitor IINon-inhibitor0.8076
Renal organic cation transporterNon-inhibitor0.8845
CYP450 2C9 substrateNon-substrate0.7229
CYP450 2D6 substrateNon-substrate0.8064
CYP450 3A4 substrateNon-substrate0.5899
CYP450 1A2 substrateInhibitor0.7936
CYP450 2C9 inhibitorInhibitor0.6712
CYP450 2D6 inhibitorNon-inhibitor0.8662
CYP450 2C19 inhibitorInhibitor0.734
CYP450 3A4 inhibitorNon-inhibitor0.7441
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6509
Ames testNon AMES toxic0.7486
CarcinogenicityNon-carcinogens0.8601
BiodegradationNot ready biodegradable0.9401
Rat acute toxicity2.3811 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9964
hERG inhibition (predictor II)Non-inhibitor0.9192
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (42.2 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03xr-0292000000-d8e012f875d1014fe351

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Xanthine oxidase activity
Specific Function
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Ha...
Gene Name
XDH
Uniprot ID
P47989
Uniprot Name
Xanthine dehydrogenase/oxidase
Molecular Weight
146422.99 Da
References
  1. Saban-Ruiz J, Alonso-Pacho A, Fabregate-Fuente M, de la Puerta Gonzalez-Quevedo C: Xanthine oxidase inhibitor febuxostat as a novel agent postulated to act against vascular inflammation. Antiinflamm Antiallergy Agents Med Chem. 2013;12(1):94-9. [Article]
  2. Nishino T, Okamoto K: Mechanistic insights into xanthine oxidoreductase from development studies of candidate drugs to treat hyperuricemia and gout. J Biol Inorg Chem. 2015 Mar;20(2):195-207. doi: 10.1007/s00775-014-1210-x. Epub 2014 Dec 12. [Article]
  3. Pohar S, Murphy G: Febuxostat for prevention of gout attacks. Issues Emerg Health Technol. 2006 Aug;(87):1-4. [Article]
  4. 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. [Article]
  5. FDA Approved Products: Uloric (febuxostat) oral tablets [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. FDA Approved Products: Uloric (febuxostat) oral tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 Da
References
  1. FDA Approved Products: Uloric (febuxostat) oral tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. FDA Approved Products: Uloric (febuxostat) oral tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. FDA Approved Products: Uloric (febuxostat) oral tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. FDA Approved Products: Uloric (febuxostat) oral tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. FDA Approved Products: Uloric (febuxostat) oral tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. FDA Approved Products: Uloric (febuxostat) oral tablets [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Mukoyoshi M, Nishimura S, Hoshide S, Umeda S, Kanou M, Taniguchi K, Muroga H: 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. doi: 10.1080/00498250801956350. [Article]
  2. FDA Approved Products: Uloric (febuxostat) oral tablets [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Miyata H, Takada T, Toyoda Y, Matsuo H, Ichida K, Suzuki H: Identification of Febuxostat as a New Strong ABCG2 Inhibitor: Potential Applications and Risks in Clinical Situations. Front Pharmacol. 2016 Dec 27;7:518. doi: 10.3389/fphar.2016.00518. eCollection 2016. [Article]
  2. Ito F, Miura M, Fujioka Y, Abumiya M, Kobayashi T, Takahashi S, Yoshioka T, Kameoka Y, Takahashi N: The BCRP inhibitor febuxostat enhances the effect of nilotinib by regulation of intracellular concentration. Int J Hematol. 2021 Jan;113(1):100-105. doi: 10.1007/s12185-020-03000-x. Epub 2020 Oct 6. [Article]
  3. Lehtisalo M, Keskitalo JE, Tornio A, Lapatto-Reiniluoto O, Deng F, Jaatinen T, Viinamaki J, Neuvonen M, Backman JT, Niemi M: Febuxostat, But Not Allopurinol, Markedly Raises the Plasma Concentrations of the Breast Cancer Resistance Protein Substrate Rosuvastatin. Clin Transl Sci. 2020 Nov;13(6):1236-1243. doi: 10.1111/cts.12809. Epub 2020 May 26. [Article]

Drug created on October 18, 2007 23:30 / Updated on June 12, 2021 01:53