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Identification
NameDeferiprone
Accession NumberDB08826
TypeSmall Molecule
GroupsApproved
DescriptionDeferiprone is an oral iron chelator used as a second line agent in thalassemia syndromes when iron overload from blood transfusions occurs. Thalassemias are a type of hereditary anaemia due a defect in the production of hemoglobin. As a result, erythropoiesis, the production of new red blood cells, is impaired. FDA approved on October 14, 2011.
Structure
Thumb
Synonyms
1,2-Dimethyl-3-hydroxypyrid-4-one
3-Hydroxy-1,2-dimethyl-4(1H)-pyridone
APO-066
CP-20
Deferipron
Deferiprona
Défériprone
Deferiproni
Deferipronum
Deferypron
Dimethylhydroxypyridone
DN-180-01-AF
Ferriprox
PL-1
External Identifiers
  • L-1
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FerriproxSolution100 mg/mlOralApotex Europe Bv1999-08-25Not applicableEu
FerriproxTablet, film coated500 mg/1OralApo Pharma Usa, Inc.2011-11-25Not applicableUs
FerriproxSolution100 mgOralApopharma Inc2016-07-28Not applicableCanada
FerriproxTablet, film coated1000 mgOralApotex Europe Bv1999-08-25Not applicableEu
FerriproxSolution100 mg/mLOralApo Pharma Usa, Inc.2015-09-09Not applicableUs
FerriproxTablet, film coated500 mgOralApotex Europe Bv1999-08-25Not applicableEu
FerriproxTablet, film coated1000 mgOralApotex Europe Bv1999-08-25Not applicableEu
FerriproxTablet1000 mgOralApopharma Inc2015-04-28Not applicableCanada
FerriproxSolution100 mg/mlOralApotex Europe Bv1999-08-25Not applicableEu
FerriproxTablet, film coated1000 mgOralApotex Europe Bv1999-08-25Not applicableEu
FerriproxTablet500 mgOralApopharma Inc2016-03-21Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII2BTY8KH53L
CAS number30652-11-0
WeightAverage: 139.1519
Monoisotopic: 139.063328537
Chemical FormulaC7H9NO2
InChI KeyTZXKOCQBRNJULO-UHFFFAOYSA-N
InChI
InChI=1S/C7H9NO2/c1-5-7(10)6(9)3-4-8(5)2/h3-4,10H,1-2H3
IUPAC Name
3-hydroxy-1,2-dimethyl-1,4-dihydropyridin-4-one
SMILES
CN1C=CC(=O)C(O)=C1C
Pharmacology
IndicationDeferiprone is indicated in thalassemia syndromes when first line chelation agents are not adequate to treat transfusional iron overload.
Structured Indications
PharmacodynamicsNot Available
Mechanism of actionDeferiprone is an iron chelator that binds to ferric ions (iron III) and forms a 3:1 (deferiprone:iron) stable complex and is then eliminated in the urine. Deferiprone is more selective for iron in which other metals such as zinc, copper, and aluminum have a lower affinity for deferiprone.
Related Articles
AbsorptionDeferiprone is absorbed in the upper gastrointestinal tract. Absorption is rapid with maximum plasma concentrations occurring after 1 hour in the fasted state and after 2 hours in the fed state.
Volume of distribution

In healthy patients, the volume of distribution is 1L/kg, and in thalassemia patients, the volume of distribution is 1.6L/kg.

Protein bindingPlasma protein binding is less than 10%.
Metabolism

Deferiprone is mainly metabolized by UGT1A6 to the 3-O-glucuronide metabolite. This metabolite cannot chelate iron.

Route of eliminationWithin 5-6 hours of administration, more than 90% of deferiprone is eliminated from the plasma. 75 to 90% of deferiprone is excreted in the urine as the metabolite.
Half lifeThe half-life is 1.9 hours.
ClearanceNot Available
ToxicityAgranulocytosis and neutropenia may occur, which can lead to fatal infections. Hepatoxicity is also possible. Most common side effects that lead to discontinuation of therapy were the gastrointestinal adverse effects (diarrhea, ulcer, nausea, gastrointestinal disturbances)
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
Aluminum hydroxideThe serum concentration of Deferiprone can be decreased when it is combined with Aluminum hydroxide.Approved
Aluminum phosphateThe serum concentration of Deferiprone can be decreased when it is combined with Aluminum phosphate.Approved
Bismuth SubcitrateThe serum concentration of Deferiprone can be decreased when it is combined with Bismuth Subcitrate.Approved
CalciumThe serum concentration of Deferiprone can be decreased when it is combined with Calcium.Nutraceutical
Calcium AcetateThe serum concentration of Deferiprone can be decreased when it is combined with Calcium Acetate.Approved
Calcium carbonateThe serum concentration of Deferiprone can be decreased when it is combined with Calcium carbonate.Approved
Calcium ChlorideThe serum concentration of Deferiprone can be decreased when it is combined with Calcium Chloride.Approved
Calcium citrateThe serum concentration of Deferiprone can be decreased when it is combined with Calcium citrate.Approved
Calcium glubionateThe serum concentration of Deferiprone can be decreased when it is combined with Calcium glubionate.Approved
Calcium GluceptateThe serum concentration of Deferiprone can be decreased when it is combined with Calcium Gluceptate.Approved
Calcium gluconateThe serum concentration of Deferiprone can be decreased when it is combined with Calcium gluconate.Approved, Vet Approved
Ferric CarboxymaltoseThe serum concentration of Deferiprone can be decreased when it is combined with Ferric Carboxymaltose.Approved
Ferric CitrateThe serum concentration of Deferiprone can be decreased when it is combined with Ferric Citrate.Approved
Ferric pyrophosphateThe serum concentration of Deferiprone can be decreased when it is combined with Ferric pyrophosphate.Approved
IronThe serum concentration of Deferiprone can be decreased when it is combined with Iron.Approved
Iron DextranThe serum concentration of Deferiprone can be decreased when it is combined with Iron Dextran.Approved, Vet Approved
Iron saccharateThe serum concentration of Deferiprone can be decreased when it is combined with Iron saccharate.Approved
MagaldrateThe serum concentration of Deferiprone can be decreased when it is combined with Magaldrate.Withdrawn
Magnesium carbonateThe serum concentration of Deferiprone can be decreased when it is combined with Magnesium carbonate.Approved
Magnesium hydroxideThe serum concentration of Deferiprone can be decreased when it is combined with Magnesium hydroxide.Approved
Magnesium oxideThe serum concentration of Deferiprone can be decreased when it is combined with Magnesium oxide.Approved
Magnesium salicylateThe serum concentration of Deferiprone can be decreased when it is combined with Magnesium salicylate.Approved
Magnesium SulfateThe serum concentration of Deferiprone can be decreased when it is combined with Magnesium Sulfate.Approved, Vet Approved
Magnesium TrisilicateThe serum concentration of Deferiprone can be decreased when it is combined with Magnesium Trisilicate.Approved
TroglitazoneThe serum concentration of Deferiprone can be increased when it is combined with Troglitazone.Withdrawn
Food Interactions
  • Food does not affect absorption.
References
Synthesis ReferenceNot Available
General References
  1. Roberts DJ, Brunskill SJ, Doree C, Williams S, Howard J, Hyde CJ: Oral deferiprone for iron chelation in people with thalassaemia. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004839. [PubMed:17636775 ]
  2. Victor Hoffbrand A: Deferiprone therapy for transfusional iron overload. Best Pract Res Clin Haematol. 2005 Jun;18(2):299-317. [PubMed:15737892 ]
External Links
ATC CodesV03AC02
AHFS Codes
  • 64:00
PDB EntriesNot Available
FDA labelDownload (287 KB)
MSDSDownload (76.7 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9803
Blood Brain Barrier+0.9381
Caco-2 permeable+0.8866
P-glycoprotein substrateNon-substrate0.7895
P-glycoprotein inhibitor INon-inhibitor0.9143
P-glycoprotein inhibitor IINon-inhibitor0.9156
Renal organic cation transporterNon-inhibitor0.8293
CYP450 2C9 substrateNon-substrate0.7463
CYP450 2D6 substrateNon-substrate0.7407
CYP450 3A4 substrateNon-substrate0.5587
CYP450 1A2 substrateNon-inhibitor0.8281
CYP450 2C9 inhibitorNon-inhibitor0.9871
CYP450 2D6 inhibitorNon-inhibitor0.9504
CYP450 2C19 inhibitorNon-inhibitor0.982
CYP450 3A4 inhibitorNon-inhibitor0.9726
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9069
Ames testNon AMES toxic0.7697
CarcinogenicityNon-carcinogens0.9563
BiodegradationReady biodegradable0.5188
Rat acute toxicity1.8734 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9539
hERG inhibition (predictor II)Non-inhibitor0.8564
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
SolutionOral100 mg/mL
SolutionOral100 mg
TabletOral1000 mg
TabletOral500 mg
Tablet, film coatedOral1000 mg
Tablet, film coatedOral500 mg/1
Tablet, film coatedOral500 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7049328 No2001-06-282021-06-28Us
US8703156 No2009-10-292029-10-29Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point272-278Not Available
water solubilityMaximum water solubility of 16–18 g/L at 24°Not Available
pKa3.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility273.0 mg/mLALOGPS
logP-0.6ALOGPS
logP0.61ChemAxon
logS0.29ALOGPS
pKa (Strongest Acidic)11.82ChemAxon
pKa (Strongest Basic)0.52ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area40.54 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity40.7 m3·mol-1ChemAxon
Polarizability14.05 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as methylpyridines. These are organic compounds containing a pyridine ring substituted at one or more positions by a methyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassMethylpyridines
Direct ParentMethylpyridines
Alternative Parents
Substituents
  • Methylpyridine
  • Hydroxypyridine
  • Dihydropyridine
  • Hydropyridine
  • Heteroaromatic compound
  • Vinylogous amide
  • Cyclic ketone
  • Azacycle
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Protein homodimerization activity
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 3 lacks transferase activity but acts as a negative regulator of isoform 1 (By similarity).
Gene Name:
UGT1A6
Uniprot ID:
P19224
Molecular Weight:
60750.215 Da
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Drug created on December 28, 2012 12:38 / Updated on December 03, 2016 02:47