Details of the Drug

General Information of Drug (ID: DM6VZFQ)

• Drug Name: Pirfenidone
• Synonyms: Deskar; Esbriet; Pirespa; Pirfenidona; Pirfenidonum; AMR 69; P 2116; AMR-69; F-647; KS-5041; Pirfenidona [INN-Spanish]; Pirfenidone (Deskar); Pirfenidone [USAN:INN]; Pirfenidonum [INN-Latin]; S-7701; Pirfenidone (JAN/USAN/INN); 5-Methyl-1-phenyl-1H-pyridin-2-one; 5-Methyl-1-phenyl-2(1H)-pyridone; 5-Methyl-1-phenyl-2-(1H)-pyridone; 5-methyl-1-phenylpyridin-2(1H)-one; 5-methyl-1-phenylpyridin-2-one

Indication

Disease Entry	ICD 11	Status	REF
Idiopathic pulmonary fibrosis	CB03.4	Approved	[1]

• Affected Organisms: Humans and other mammals
• ATC Code:
  L04AX05: Pirfenidone
  L04AX: Other immunosuppressants
  L04A: IMMUNOSUPPRESSANTS
  L04: IMMUNOSUPPRESSANTS
  L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 185.22
  Logarithm of the Partition Coefficient (xlogp); 1.9
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 1
• ADMET Property:
  Absorption: The drug is rapidly absorbed following oral administration []
  Half-life: The concentration or amount of drug in body reduced by one-half in 2 - 2.5 hours [2]
  Vd: The volume of distribution (Vd) of drug is 70 L [3]
• Chemical Identifiers:
  Formula: C12H11NO
  IUPAC Name: 5-methyl-1-phenylpyridin-2-one
  Canonical SMILES: CC1=CN(C(=O)C=C1)C2=CC=CC=C2
  InChI: InChI=1S/C12H11NO/c1-10-7-8-12(14)13(9-10)11-5-3-2-4-6-11/h2-9H,1H3
  InChIKey: ISWRGOKTTBVCFA-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 40632
  ChEBI ID: CHEBI:32016
  CAS Number: 53179-13-8
  UNII: D7NLD2JX7U
  DrugBank ID: DB04951
  TTD ID: D02WCI
  INTEDE ID: DR1299
  ACDINA ID: D00536

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Transforming growth factor beta 1 (TGFB1)	TTR9XHZ	TGFB1_HUMAN	Modulator	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A2 (CYP1A2) Main DME	DEJGDUW	CP1A2_HUMAN	Substrate	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Gene/Protein Processing	[6]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Gene/Protein Processing	[7]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Gene/Protein Processing	[8]
Histone deacetylase 9 (HDAC9)	OTO8O0LF	HDAC9_HUMAN	Gene/Protein Processing	[7]

Molecular Expression Atlas of This Drug

• The Studied Disease: Idiopathic pulmonary fibrosis
• ICD Disease Classification: CB03.4

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Transforming growth factor beta 1 (TGFB1)	DTT	TGFB1	5.95E-09	1.68	7.81
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	7.68E-02	-2.10E-01	-6.42E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Pirfenidone (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Pirfenidone and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[9]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Pirfenidone and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[10]
Obeticholic acid	DM3Q1SM	Moderate	Decreased metabolism of Pirfenidone caused by Obeticholic acid mediated inhibition of CYP450 enzyme.	Autoimmune liver disease [DB96]	[11]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Pirfenidone and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[12]
Osilodrostat	DMIJC9X	Major	Decreased metabolism of Pirfenidone caused by Osilodrostat mediated inhibition of CYP450 enzyme.	Cushing syndrome [5A70]	[9]
Ivacaftor	DMZC1HS	Moderate	Decreased metabolism of Pirfenidone caused by Ivacaftor mediated inhibition of CYP450 enzyme.	Cystic fibrosis [CA25]	[13]
MK-8228	DMOB58Q	Moderate	Increased metabolism of Pirfenidone caused by MK-8228 mediated induction of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[14]
Cenobamate	DM8KLU9	Moderate	Decreased metabolism of Pirfenidone caused by Cenobamate mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[11]
Stiripentol	DMMSDOY	Moderate	Decreased metabolism of Pirfenidone caused by Stiripentol mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[11]
Eslicarbazepine	DMZREFQ	Moderate	Decreased metabolism of Pirfenidone caused by Eslicarbazepine mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[11]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Pirfenidone and Cannabidiol.	Epileptic encephalopathy [8A62]	[11]
Mirabegron	DMS1GYT	Moderate	Decreased metabolism of Pirfenidone caused by Mirabegron mediated inhibition of CYP450 enzyme.	Functional bladder disorder [GC50]	[11]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Pirfenidone and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[15]
Etravirine	DMGV8QU	Moderate	Decreased metabolism of Pirfenidone caused by Etravirine mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[11]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Pirfenidone and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[16]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Pirfenidone and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[17]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Pirfenidone and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[18]
Givosiran	DM5PFIJ	Major	Decreased metabolism of Pirfenidone caused by Givosiran mediated inhibition of CYP450 enzyme.	Inborn porphyrin/heme metabolism error [5C58]	[9]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Pirfenidone caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[19]
Glycerol phenylbutyrate	DMDGRQO	Moderate	Decreased metabolism of Pirfenidone caused by Glycerol phenylbutyrate mediated inhibition of CYP450 enzyme.	Liver disease [DB90-DB9Z]	[11]
Ceritinib	DMB920Z	Moderate	Decreased metabolism of Pirfenidone caused by Ceritinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[9]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Pirfenidone caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[9]
Dacomitinib	DMOH8VY	Moderate	Decreased metabolism of Pirfenidone caused by Dacomitinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[11]
Capmatinib	DMYCXKL	Major	Decreased metabolism of Pirfenidone caused by Capmatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[9]
Lumefantrine	DM29GAD	Moderate	Decreased metabolism of Pirfenidone caused by Lumefantrine mediated inhibition of CYP450 enzyme.	Malaria [1F40-1F45]	[11]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Pirfenidone and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[20]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Pirfenidone and Idelalisib.	Mature B-cell leukaemia [2A82]	[21]
Vemurafenib	DM62UG5	Major	Decreased metabolism of Pirfenidone caused by Vemurafenib mediated inhibition of CYP450 enzyme.	Melanoma [2C30]	[9]
Panobinostat	DM58WKG	Moderate	Decreased metabolism of Pirfenidone caused by Panobinostat mediated inhibition of CYP450 enzyme.	Multiple myeloma [2A83]	[11]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Pirfenidone caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[11]
Rolapitant	DM8XP26	Moderate	Decreased metabolism of Pirfenidone caused by Rolapitant mediated inhibition of CYP450 enzyme.	Nausea/vomiting [MD90]	[11]
Rucaparib	DM9PVX8	Major	Decreased metabolism of Pirfenidone caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[9]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Pirfenidone caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[22]
Lonafarnib	DMGM2Z6	Moderate	Decreased metabolism of Pirfenidone caused by Lonafarnib mediated inhibition of CYP450 enzyme.	Premature ageing appearance [LD2B]	[11]
ABIRATERONE	DM8V75C	Moderate	Decreased metabolism of Pirfenidone caused by ABIRATERONE mediated inhibition of CYP450 enzyme.	Prostate cancer [2C82]	[11]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Pirfenidone and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[11]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Ammonia	E00007	222	Alkalizing agent
Carmellose sodium	E00625	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 3350	E00652	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Vinylpyrrolidone	E00668	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Pirfenidone 801 mg tablet	801 mg	Oral Tablet	Oral
Pirfenidone 267 mg tablet	267 mg	Oral Tablet	Oral
Pirfenidone 267 mg capsule	267 mg	Oral Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7532).
• [2] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [3] Health Canada Product Monograph: Esbriet (pirfenidone) for oral use
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Risk of clinically relevant pharmacokinetic-based drug-drug interactions with drugs approved by the U.S. Food and Drug Administration between 2013 and 2016. Drug Metab Dispos. 2018 Jun;46(6):835-845.
• [6] Targeting the myofibroblast genetic switch: inhibitors of myocardin-related transcription factor/serum response factor-regulated gene transcription prevent fibrosis in a murine model of skin injury. J Pharmacol Exp Ther. 2014 Jun;349(3):480-6. doi: 10.1124/jpet.114.213520. Epub 2014 Apr 4.
• [7] Comparison of the antifibrotic effects of the pan-histone deacetylase-inhibitor panobinostat versus the IPF-drug pirfenidone in fibroblasts from patients with idiopathic pulmonary fibrosis. PLoS One. 2018 Nov 27;13(11):e0207915. doi: 10.1371/journal.pone.0207915. eCollection 2018.
• [8] Human precision-cut liver slices as a model to test antifibrotic drugs in the early onset of liver fibrosis. Toxicol In Vitro. 2016 Sep;35:77-85. doi: 10.1016/j.tiv.2016.05.012. Epub 2016 May 26.
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• [13] Product Information. Kalydeco (ivacaftor). Vertex Pharmaceuticals, Cambridge, MA.
• [14] Product Information. Prevymis (letermovir). Merck & Company Inc, Whitehouse Station, NJ.
• [15] Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
• [16] Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
• [17] Canadian Pharmacists Association.
• [18] Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
• [19] Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
• [20] Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
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