Pirfenidone

Identification

Summary

Pirfenidone is an agent used for the treatment of idiopathic pulmonary fibrosis (IPF).

Brand Names
Esbriet
Generic Name
Pirfenidone
DrugBank Accession Number
DB04951
Background

Pirfenidone is an orally active small molecule drug that may inhibit collagen synthesis, down regulate production of multiple cytokines and block fibroblast proliferation and stimulation in response to cytokines. Pirfenidone has demonstrated activity in multiple fibrotic conditions, including those of the lung, kidney and liver. It is being investigated by InterMune.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 185.2218
Monoisotopic: 185.084063979
Chemical Formula
C12H11NO
Synonyms
  • Pirfenidona
  • Pirfenidone
External IDs
  • AMR-69

Pharmacology

Indication

For the treatment of idiopathic pulmonary fibrosis (IPF).

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Pirfenidone is a novel agent with anti-inflammatory, antioxidant, and antifibrotic properties. It may improve lung function and reduce the number of acute exacerbations in patients with idiopathic pulmonary fibrosis (IPF).

Mechanism of action

Although the precise mechanism of action of pirfenidone and its specific molecular targets have yet to be elucidated6,7, the molecule has demonstrated anti-fibrotic, anti-inflammatory, and antioxidant activity.3,5 One vital anti-fibrotic mechanism involves suppression of TGF-β1 (transforming growth factor-β1), a key cytokine involved in fibrogenesis and extracellular matrix production.3,4,5,6

There is also evidence to suggest that pirfenidone has the ability to downregulate the expression of potent pro-inflammatory cytokines including TNF-α, interleukin-1, and interferon gamma.3,5 In animal models, pirfenidone can inhibit both the influx of inflammatory cells and the increased pulmonary vascular permeability induced by bleomycin.3

Absorption

Rapidly absorbed following oral administration.

Volume of distribution

The steady-state volume of distribution following oral administration is approximately 70L.8

Protein binding

Pirfenidone is 50-58% protein-bound in plasma, primarily to albumin.8

Metabolism

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Route of elimination

Not Available

Half-life

2-2.5 hours

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Generally well tolerated with the most frequent side effects reported being photosensitivity rash and gastrointestinal symptoms.

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
AbametapirThe serum concentration of Pirfenidone can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Pirfenidone can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Pirfenidone can be increased when it is combined with Abiraterone.
AcenocoumarolThe metabolism of Pirfenidone can be decreased when combined with Acenocoumarol.
AcetaminophenThe metabolism of Pirfenidone can be decreased when combined with Acetaminophen.
AcyclovirThe metabolism of Pirfenidone can be decreased when combined with Acyclovir.
AdalimumabThe metabolism of Pirfenidone can be increased when combined with Adalimumab.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Pirfenidone.
AgomelatineThe metabolism of Agomelatine can be decreased when combined with Pirfenidone.
AlbendazoleThe serum concentration of Pirfenidone can be decreased when it is combined with Albendazole.
Interactions
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Food Interactions
  • Take at the same time every day.
  • Take with food. This may reduce the adverse effects of nausea and dizziness. Food also impacts the bioavailability of pirfenidone.

Products

Products2
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EsbrietTablet, film coated534 mgOralRoche Registration Gmb H2020-12-16Not applicableEU flag
EsbrietCapsule267 mg/1OralInter Mune2014-10-16Not applicableUS flag
EsbrietTablet267 mgOralHoffmann La Roche2017-07-26Not applicableCanada flag
EsbrietTablet, film coated267 mgOralRoche Registration Gmb H2020-12-16Not applicableEU flag
EsbrietTablet, film coated267 mgOralRoche Registration Gmb H2020-12-16Not applicableEU flag
EsbrietTablet, film coated267 mgOralRoche Registration Gmb H2020-12-16Not applicableEU flag
EsbrietCapsule267 mgOralRoche Registration Gmb H2016-09-08Not applicableEU flag
EsbrietTablet, film coated267 mgOralRoche Registration Gmb H2020-12-16Not applicableEU flag
EsbrietTablet, coated267 mg/1OralGenentech, Inc.2017-01-11Not applicableUS flag
EsbrietTablet, film coated801 mgOralRoche Registration Gmb H2020-12-16Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Jamp PirfenidoneCapsule267 mgOralJamp Pharma Corporation2021-06-04Not applicableCanada flag
Jamp PirfenidoneTablet801 mgOralJamp Pharma CorporationNot applicableNot applicableCanada flag
Jamp PirfenidoneTablet267 mgOralJamp Pharma CorporationNot applicableNot applicableCanada flag
Sandoz Pirfenidone CapsulesCapsule267 mgOralSandoz Canada IncorporatedNot applicableNot applicableCanada flag
Sandoz Pirfenidone TabletsTablet267 mgOralSandoz Canada Incorporated2021-05-04Not applicableCanada flag
Sandoz Pirfenidone TabletsTablet801 mgOralSandoz Canada Incorporated2021-05-04Not applicableCanada flag
Teva-pirfenidoneTablet801 mgOralTEVA Canada LimitedNot applicableNot applicableCanada flag
Teva-pirfenidoneTablet267 mgOralTEVA Canada LimitedNot applicableNot applicableCanada flag

Categories

ATC Codes
L04AX05 — Pirfenidone
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pyridinones. These are compounds containing a pyridine ring, which bears a ketone.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Hydropyridines
Direct Parent
Pyridinones
Alternative Parents
Methylpyridines / Dihydropyridines / Benzene and substituted derivatives / Heteroaromatic compounds / Lactams / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organic oxides
show 1 more
Substituents
Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Dihydropyridine / Heteroaromatic compound / Hydrocarbon derivative / Lactam / Methylpyridine / Monocyclic benzene moiety / Organic nitrogen compound
show 6 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
ring assembly, pyridone (CHEBI:32016)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
D7NLD2JX7U
CAS number
53179-13-8
InChI Key
ISWRGOKTTBVCFA-UHFFFAOYSA-N
InChI
InChI=1S/C12H11NO/c1-10-7-8-12(14)13(9-10)11-5-3-2-4-6-11/h2-9H,1H3
IUPAC Name
5-methyl-1-phenyl-1,2-dihydropyridin-2-one
SMILES
CC1=CN(C(=O)C=C1)C1=CC=CC=C1

References

General References
  1. Hale ML, Margolin SB, Krakauer T, Roy CJ, Stiles BG: Pirfenidone blocks the in vitro and in vivo effects of staphylococcal enterotoxin B. Infect Immun. 2002 Jun;70(6):2989-94. [Article]
  2. Shi S, Wu J, Chen H, Chen H, Wu J, Zeng F: Single- and multiple-dose pharmacokinetics of pirfenidone, an antifibrotic agent, in healthy Chinese volunteers. J Clin Pharmacol. 2007 Oct;47(10):1268-76. [Article]
  3. Cho ME, Kopp JB: Pirfenidone: an anti-fibrotic therapy for progressive kidney disease. Expert Opin Investig Drugs. 2010 Feb;19(2):275-83. doi: 10.1517/13543780903501539. [Article]
  4. Biernacka A, Dobaczewski M, Frangogiannis NG: TGF-beta signaling in fibrosis. Growth Factors. 2011 Oct;29(5):196-202. doi: 10.3109/08977194.2011.595714. Epub 2011 Jul 11. [Article]
  5. Ruwanpura SM, Thomas BJ, Bardin PG: Pirfenidone: Molecular Mechanisms and Potential Clinical Applications in Lung Disease. Am J Respir Cell Mol Biol. 2020 Apr;62(4):413-422. doi: 10.1165/rcmb.2019-0328TR. [Article]
  6. Ballester B, Milara J, Cortijo J: Pirfenidone anti-fibrotic effects are partially mediated by the inhibition of MUC1 bioactivation. Oncotarget. 2020 Apr 14;11(15):1306-1320. doi: 10.18632/oncotarget.27526. eCollection 2020 Apr 14. [Article]
  7. FDA Approved Drug Products: Esbriet (pirfenidone) for oral use [Link]
  8. Health Canada Product Monograph: Esbriet (pirfenidone) for oral use [Link]
  9. CaymanChem: Pirfenidone MSDS [Link]
PubChem Compound
40632
PubChem Substance
175426915
ChemSpider
37115
BindingDB
50005201
RxNav
1592254
ChEBI
32016
ChEMBL
CHEMBL1256391
ZINC
ZINC000000001958
Wikipedia
Pirfenidone

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)3
4RecruitingTreatmentConnective Tissue Diseases / Interstitial Lung Diseases (ILD) / Pirfenidone1
4RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19) / Novel Coronavirus-induced Lung Fibrosis1
4RecruitingTreatmentProgressive Idiopathic Pulmonary Fibrosis1
4Unknown StatusTreatmentAcute Kidney Injury (AKI) / Septic1
4Unknown StatusTreatmentDermatopolymyositis / Interstitial Lung Diseases (ILD)1
4Unknown StatusTreatmentSarcoidosis, Pulmonary1
3Active Not RecruitingTreatmentAlbuminuria / Diabetic Nephropathy1
3CompletedTreatmentDiabetic Foot Ulcers (DFUs)1
3CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)5

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral
CapsuleOral267 MG
CapsuleOral267 mg/1
TabletOral267 mg
Tablet, coatedOral267 mg/1
Tablet, coatedOral801 mg/1
Tablet, film coatedOral534 MG
Tablet, film coatedOral267 mg
Tablet, film coatedOral801 mg
Capsule, coatedOral267 mg
TabletOral801 mg
Tablet, film coatedOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7988994No2011-08-022026-09-22US flag
US7816383No2010-10-192030-01-08US flag
US8013002No2011-09-062030-01-08US flag
US8084475No2011-12-272030-01-08US flag
US8778947No2014-07-152033-08-30US flag
US7566729No2009-07-282029-04-22US flag
US7767225No2010-08-032026-09-22US flag
US7635707No2009-12-222029-04-22US flag
US7767700No2010-08-032027-12-18US flag
US8592462No2013-11-262029-04-22US flag
US8383150No2013-02-262026-09-22US flag
US8318780No2012-11-272030-01-08US flag
US8420674No2013-04-162027-12-18US flag
US7910610No2011-03-222030-01-08US flag
US8648098No2014-02-112030-01-08US flag
US8754109No2014-06-172030-01-08US flag
US8609701No2013-12-172029-04-22US flag
US8753679No2014-06-172026-09-22US flag
US7696236No2010-04-132027-12-18US flag
US9561217No2017-02-072022-01-25US flag
US10188637No2019-01-292037-03-28US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.89 mg/mLALOGPS
logP2ALOGPS
logP2.14ChemAxon
logS-1.8ALOGPS
pKa (Strongest Basic)-1.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area20.31 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity57 m3·mol-1ChemAxon
Polarizability20.28 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9932
Blood Brain Barrier+0.996
Caco-2 permeable+0.8614
P-glycoprotein substrateNon-substrate0.8193
P-glycoprotein inhibitor INon-inhibitor0.755
P-glycoprotein inhibitor IINon-inhibitor0.9177
Renal organic cation transporterNon-inhibitor0.8157
CYP450 2C9 substrateNon-substrate0.6638
CYP450 2D6 substrateNon-substrate0.8248
CYP450 3A4 substrateSubstrate0.6111
CYP450 1A2 substrateInhibitor0.9108
CYP450 2C9 inhibitorNon-inhibitor0.5982
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.7166
CYP450 3A4 inhibitorNon-inhibitor0.775
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7633
Ames testNon AMES toxic0.7652
CarcinogenicityNon-carcinogens0.8992
BiodegradationNot ready biodegradable0.9112
Rat acute toxicity2.1330 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9784
hERG inhibition (predictor II)Non-inhibitor0.6301
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-2900000000-b9809376eba9769e9bee

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Arai T, Inoue Y, Sasaki Y, Tachibana K, Nakao K, Sugimoto C, Okuma T, Akira M, Kitaichi M, Hayashi S: Predictors of the clinical effects of pirfenidone on idiopathic pulmonary fibrosis. Respir Investig. 2014 Mar;52(2):136-43. doi: 10.1016/j.resinv.2013.09.002. Epub 2013 Oct 24. [Article]
  2. Health Canada Product Monograph: Esbriet (pirfenidone) for oral use [Link]
  3. Pirfenidone FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Health Canada Product Monograph: Esbriet (pirfenidone) for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Health Canada Product Monograph: Esbriet (pirfenidone) for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Health Canada Product Monograph: Esbriet (pirfenidone) for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Health Canada Product Monograph: Esbriet (pirfenidone) for oral use [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. Health Canada Product Monograph: Esbriet (pirfenidone) for oral use [Link]

Drug created on October 21, 2007 22:23 / Updated on September 16, 2021 13:04