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
Structure for Pirfenidone (DB04951)
- 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).
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- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- 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
Hover over products below to view reaction partners
- Route of elimination
Not Available
- Half-life
2-2.5 hours
- Clearance
Not Available
- Adverse Effects
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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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Pirfenidone can be increased when it is combined with Abametapir. Abatacept The metabolism of Pirfenidone can be increased when combined with Abatacept. Abiraterone The serum concentration of Pirfenidone can be increased when it is combined with Abiraterone. Acenocoumarol The metabolism of Pirfenidone can be decreased when combined with Acenocoumarol. Acetaminophen The metabolism of Pirfenidone can be decreased when combined with Acetaminophen. Acyclovir The metabolism of Pirfenidone can be decreased when combined with Acyclovir. Adalimumab The metabolism of Pirfenidone can be increased when combined with Adalimumab. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Pirfenidone. Agomelatine The metabolism of Agomelatine can be decreased when combined with Pirfenidone. Albendazole The serum concentration of Pirfenidone can be decreased when it is combined with Albendazole. 
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- 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
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Esbriet Capsule Oral Roche Registration Gmb H 2016-09-08 Not applicable EU 
Esbriet Tablet, film coated Oral Roche Registration Gmb H 2020-12-16 Not applicable EU Esbriet Tablet, film coated Oral Roche Registration Gmb H 2020-12-16 Not applicable EU Esbriet Capsule 267 mg/1 Oral Genentech, Inc. 2014-10-15 Not applicable US 
Esbriet Tablet, film coated Oral Roche Registration Gmb H 2020-12-16 Not applicable EU Esbriet Tablet, film coated Oral Roche Registration Gmb H 2020-12-16 Not applicable EU Esbriet Tablet, film coated Oral Roche Registration Gmb H 2020-12-16 Not applicable EU Esbriet Tablet, film coated Oral Roche Registration Gmb H 2020-12-16 Not applicable EU Esbriet Capsule Oral Roche Registration Gmb H 2016-09-08 Not applicable EU Esbriet Tablet, coated 801 mg/1 Oral Genentech, Inc. 2017-01-11 Not applicable US
Categories
- ATC Codes
- L04AX05 — Pirfenidone
- Drug Categories
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antifibrotic Agents
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Antirheumatic Agents
- Central Nervous System Agents
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2E1 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Immunosuppressive Agents
- Peripheral Nervous System Agents
- Pyridines
- Pyridones
- Sensory System Agents
- 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
- 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. [PubMed:12010989]
- 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. [PubMed:17906160]
- 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. [PubMed:20050822]
- 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. [PubMed:21740331]
- 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. [PubMed:31967851]
- 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. [PubMed:32341751]
- FDA Approved Drug Products: Esbriet (pirfenidone) for oral use [Link]
- Health Canada Product Monograph: Esbriet (pirfenidone) for oral use [Link]
- CaymanChem: Pirfenidone MSDS [Link]
- External Links
- PubChem Compound
- 40632
- PubChem Substance
- 175426915
- ChemSpider
- 37115
- BindingDB
- 50005201
- 1592254
- ChEBI
- 32016
- ChEMBL
- CHEMBL1256391
- ZINC
- ZINC000000001958
- Wikipedia
- Pirfenidone
- AHFS Codes
- 48:02.00 — Antifibrotic Agents
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Idiopathic Pulmonary Fibrosis (IPF) 3 4 Recruiting Treatment Novel Coronavirus-induced Lung Fibrosis 1 4 Recruiting Treatment Progressive Idiopathic Pulmonary Fibrosis 1 4 Unknown Status Treatment Acute Kidney Injury (AKI) / Sepsis 1 4 Unknown Status Treatment Dermatopolymyositis / Interstitial Lung Diseases (ILD) 1 4 Unknown Status Treatment Sarcoidosis, Pulmonary 1 3 Active Not Recruiting Treatment Albuminuria / Diabetic Nephropathy 1 3 Completed Treatment Diabetic Foot Ulcers (DFU) 1 3 Completed Treatment Idiopathic Pulmonary Fibrosis (IPF) 5 3 Recruiting Treatment Dermatomyositis Interstitial Lung Disease (Dm-ILD) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral Capsule Oral 267 mg/1 Capsule Oral 267 mg Tablet Oral 267 mg Tablet Oral 801 mg Tablet, coated Oral 267 mg/1 Tablet, coated Oral 801 mg/1 Tablet, film coated Oral Tablet, film coated Oral 267 mg Tablet, film coated Oral 801 mg Capsule, coated Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7988994 No 2011-08-02 2026-09-22 US US7816383 No 2010-10-19 2030-01-08 US US8013002 No 2011-09-06 2030-01-08 US US8084475 No 2011-12-27 2030-01-08 US US8778947 No 2014-07-15 2033-08-30 US US7566729 No 2009-07-28 2029-04-22 US US7767225 No 2010-08-03 2026-09-22 US US7635707 No 2009-12-22 2029-04-22 US US7767700 No 2010-08-03 2027-12-18 US US8592462 No 2013-11-26 2029-04-22 US US8383150 No 2013-02-26 2026-09-22 US US8318780 No 2012-11-27 2030-01-08 US US8420674 No 2013-04-16 2027-12-18 US US7910610 No 2011-03-22 2030-01-08 US US8648098 No 2014-02-11 2030-01-08 US US8754109 No 2014-06-17 2030-01-08 US US8609701 No 2013-12-17 2029-04-22 US US8753679 No 2014-06-17 2026-09-22 US US7696236 No 2010-04-13 2027-12-18 US US9561217 No 2017-02-07 2022-01-25 US US10188637 No 2019-01-29 2037-03-28 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 2.89 mg/mL ALOGPS logP 2 ALOGPS logP 2.14 ChemAxon logS -1.8 ALOGPS pKa (Strongest Basic) -1.2 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 1 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 20.31 Å2 ChemAxon Rotatable Bond Count 1 ChemAxon Refractivity 57 m3·mol-1 ChemAxon Polarizability 20.28 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule Yes ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9932 Blood Brain Barrier + 0.996 Caco-2 permeable + 0.8614 P-glycoprotein substrate Non-substrate 0.8193 P-glycoprotein inhibitor I Non-inhibitor 0.755 P-glycoprotein inhibitor II Non-inhibitor 0.9177 Renal organic cation transporter Non-inhibitor 0.8157 CYP450 2C9 substrate Non-substrate 0.6638 CYP450 2D6 substrate Non-substrate 0.8248 CYP450 3A4 substrate Substrate 0.6111 CYP450 1A2 substrate Inhibitor 0.9108 CYP450 2C9 inhibitor Non-inhibitor 0.5982 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.7166 CYP450 3A4 inhibitor Non-inhibitor 0.775 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7633 Ames test Non AMES toxic 0.7652 Carcinogenicity Non-carcinogens 0.8992 Biodegradation Not ready biodegradable 0.9112 Rat acute toxicity 2.1330 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9784 hERG inhibition (predictor II) Non-inhibitor 0.6301
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-000i-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
- 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. [PubMed:24636270]
- Health Canada Product Monograph: Esbriet (pirfenidone) for oral use [Link]
- 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
- 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
- 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
- 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
- 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
- Health Canada Product Monograph: Esbriet (pirfenidone) for oral use [Link]
Drug created on October 21, 2007 22:23 / Updated on May 06, 2021 06:19