Identification

Name
Deferiprone
Accession Number
DB08826
Type
Small Molecule
Groups
Approved
Description

Deferiprone 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
  • Deferipron
  • Deferiprona
  • Défériprone
  • Deferiproni
  • Deferipronum
  • Deferypron
  • Dimethylhydroxypyridone
  • PL-1
External IDs
APO-66 / CP-20 / CP20 / DN-180-01-AF / L-1
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FerriproxSolution100 mg/mlOralApotex Europe Bv1999-08-25Not applicableEu
FerriproxTablet1000 mgOralApopharma Inc2015-04-28Not applicableCanada
FerriproxSolution100 mgOralApopharma Inc2016-07-28Not applicableCanada
FerriproxTablet, film coated1000 mgOralApotex Europe Bv1999-08-25Not applicableEu
FerriproxTablet, film coated500 mgOralApotex Europe Bv1999-08-25Not applicableEu
FerriproxTablet, film coated500 mg/1OralApopharma Inc2011-11-25Not applicableUs
FerriproxTablet, film coated1000 mgOralApotex Europe Bv1999-08-25Not applicableEu
FerriproxSolution100 mg/mlOralApotex Europe Bv1999-08-25Not applicableEu
FerriproxTablet500 mgOralApopharma Inc2016-03-21Not applicableCanada
FerriproxSolution100 mg/1mLOralApopharma Inc2015-09-09Not applicableUs
International/Other Brands
Ferriprox
Categories
UNII
2BTY8KH53L
CAS number
30652-11-0
Weight
Average: 139.1519
Monoisotopic: 139.063328537
Chemical Formula
C7H9NO2
InChI Key
TZXKOCQBRNJULO-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

Indication

Deferiprone is indicated in thalassemia syndromes when first line chelation agents are not adequate to treat transfusional iron overload.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Deferiprone 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.

Absorption

Deferiprone 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 binding

Plasma 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 elimination

Within 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 life

The half-life is 1.9 hours.

Clearance
Not Available
Toxicity

Agranulocytosis 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcetaminophenAcetaminophen may decrease the excretion rate of Deferiprone which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Deferiprone which could result in a higher serum level.
Adefovir DipivoxilAdefovir Dipivoxil may decrease the excretion rate of Deferiprone which could result in a higher serum level.
AlmasilateThe serum concentration of Deferiprone can be decreased when it is combined with Almasilate.
AloglutamolThe serum concentration of Deferiprone can be decreased when it is combined with Aloglutamol.
AlprazolamAlprazolam may decrease the excretion rate of Deferiprone which could result in a higher serum level.
AluminiumThe serum concentration of Deferiprone can be decreased when it is combined with Aluminium.
Aluminium acetoacetateThe serum concentration of Deferiprone can be decreased when it is combined with Aluminium acetoacetate.
Aluminium glycinateThe serum concentration of Deferiprone can be decreased when it is combined with Aluminium glycinate.
Aluminum hydroxideAluminum hydroxide can cause a decrease in the absorption of Deferiprone resulting in a reduced serum concentration and potentially a decrease in efficacy.
Food Interactions
  • Food does not affect absorption.

References

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
KEGG Drug
D07416
PubChem Compound
2972
PubChem Substance
175427107
ChemSpider
2866
ChEBI
68554
ChEMBL
CHEMBL70927
PharmGKB
PA166118041
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Deferiprone
ATC Codes
V03AC02 — Deferiprone
AHFS Codes
  • 64:00.00 — Heavy Metal Antagonists
FDA label
Download (287 KB)
MSDS
Download (76.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0WithdrawnOtherMild Cognitive Impairment (MCI)1
1CompletedNot AvailableBioequivalence1
1CompletedNot AvailableHealthy Volunteers3
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
1CompletedNot AvailableSickle Cell Disorders1
1CompletedTreatmentHIV Infection Asymptomatic1
1CompletedTreatmentHealthy Volunteers1
1, 2Active Not RecruitingTreatmentThalassemia Major With Severe Transfusional Iron Overload1
1, 2CompletedTreatmentFriedreich's Ataxia1
2Active Not RecruitingTreatmentAcute iron intoxication / Neurodegenerative Disorders1
2CompletedSupportive CareAcute iron intoxication / Amyotrophic Lateral Sclerosis (ALS)1
2CompletedTreatmentFriedreich's Ataxia1
2CompletedTreatmentHemochromatosis1
2RecruitingTreatmentIron Overload Due to Repeated Red Blood Cell Transfusions / Myelodysplastic Syndrome With Low-grade Lesions1
2RecruitingTreatmentMild Alzheimer's Disease / Mild Cognitive Impairment (MCI) / Prodromal Alzheimer's Disease1
2RecruitingTreatmentParkinson's Disease (PD)2
2TerminatedTreatmentBeta-Thalassemia / Cardiovascular Disease (CVD) / Heart Diseases1
2Unknown StatusTreatmentParkinson's Disease (PD)1
2, 3CompletedTreatmentParkinson's Disease (PD)1
2, 3Not Yet RecruitingTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2, 3Not Yet RecruitingTreatmentDiabetes Mellitus (DM) / Gastroduodenal Ulcers / Iron Metabolism Disorders / Optic Atrophy / Platelets Dysfunction / Sensorineural Hearing Loss1
2, 3Unknown StatusTreatmentBeta Thalassemia Major1
2, 3Unknown StatusTreatmentBeta-Thalassemia Major / Iron Hemosiderosis / Sickle Cell Disorders1
2, 3Unknown StatusTreatmentIron Chelation / Thalassemia Major (TM) / Vitamin c1
3CompletedTreatmentChronic Iron Overload1
3CompletedTreatmentHemochromatosis1
3CompletedTreatmentPantothenate Kinase-associated Neurodegeneration (PKAN)2
3CompletedTreatmentAcute iron intoxication1
3Unknown StatusTreatmentAcute Kidney Injury (AKI)1
4CompletedNot AvailableHepatic Impairment1
4CompletedNot AvailableImpaired Renal Function1
4CompletedTreatmentBeta-Thalassemia / Thalassemia Major (TM)1
4CompletedTreatmentHemosiderosis / Thalassemia Major (TM)1
4CompletedTreatmentProlonged QTc Interval1
4CompletedTreatmentAcute iron intoxication / Prophylaxis of cardiomyopathy1
4Enrolling by InvitationTreatmentAcute iron intoxication / Other Anemias / Sickle Cell Disorders1
4RecruitingTreatmentAcute iron intoxication / Beta Thalassemia Major Anemia1
4RecruitingTreatmentAcute iron intoxication / Other Anemias / Sickle Cell Disorders1
4Unknown StatusTreatmentBeta-Thalassemia1
Not AvailableActive Not RecruitingBasic ScienceAcute iron intoxication / Amyotrophic Lateral Sclerosis (ALS) / Oxidative Stress / Parkinson's Disease (PD)1
Not AvailableApproved for MarketingNot AvailableAcute iron intoxication1
Not AvailableAvailableNot AvailablePantothenate Kinase-associated Neurodegeneration (PKAN)1
Not AvailableCompletedNot AvailableAcute iron intoxication / Beta-Thalassemia / Bone destruction / Hematologic Diseases / Pulmonary Hypertension (PH) / Thalassaemic disorders / Thalassemia Major (TM)1
Not AvailableCompletedTreatmentBeta-Thalassemia Major1
Not AvailableCompletedTreatmentThalassaemic disorders1
Not AvailableUnknown StatusTreatmentBeta-Thalassemia / Iron Chelation Therapy / Serum Ferritin1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionOral100 mg
SolutionOral100 mg/ml
SolutionOral100 mg/1mL
TabletOral1000 mg
TabletOral500 mg
Tablet, film coatedOral1000 mg
Tablet, film coatedOral500 mg/1
Tablet, film coatedOral500 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7049328No2001-06-282021-06-28Us
US8703156No2009-10-292029-10-29Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)272-278Not 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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
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

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Methylpyridines
Direct Parent
Methylpyridines
Alternative Parents
Hydroxypyridines / Dihydropyridines / Vinylogous amides / Heteroaromatic compounds / Cyclic ketones / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Dihydropyridine / Methylpyridine / Hydroxypyridine / Hydropyridine / Vinylogous amide / Heteroaromatic compound / Cyclic ketone / Azacycle / Organic nitrogen compound / Hydrocarbon derivative
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyridone (CHEBI:68554)

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 trans...
Gene Name
UGT1A6
Uniprot ID
P19224
Uniprot Name
UDP-glucuronosyltransferase 1-6
Molecular Weight
60750.215 Da

Drug created on December 28, 2012 12:38 / Updated on September 25, 2018 17:45