Pirfenidone

Status : investigational

Therapeutic Classification

IMMUNOSUPPRESSANTS

ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSUPPRESSANTS
IMMUNOSUPPRESSANTS

Description

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.

Used

For the treatment of idiopathic pulmonary fibrosis (IPF).

Mechanism Of Action

Pirfenidone is an orally active, small molecule that shows a wide range of biologic activity. In vitro evidence has shown that pirfenidone inhibits collagen synthesis, down-regulates profibrotic cytokines and decreases fibroblast proliferation. Pirfenidone leads to a reduction of TGF-beta2 mRNA levels and of the mature TGF-beta2 protein due to decreased expression and direct inhibition of the TGF-beta pro-protein convertase furin. In addition, pirfenidone reduces the protein levels of the matrix metalloproteinase (MMP)-11, a TGF-beta target gene and furin substrate involved in carcinogenesis.

Dosage

Form Route Strength
Capsule oral 267 mg

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).

Toxic Effect

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

Absorption

Rapidly absorbed following oral administration.

Half Life

2-2.5 hours

Chemical Classification

This compound belongs to the class of organic compounds known as pyridinones. These are compounds containing a pyridine ring, which bears a ketone.

Pyridinones

Organic compounds

Organoheterocyclic compounds

Pyridines and derivatives

Hydropyridines

Brands

name Dosage form Country
Esbriet capsule Canada
Esbriet capsule US

Drug Drug Interactions

  •  Carbamazepine  : CYP1A2 Inducers (Strong) may decrease the serum concentration of Pirfenidone.
  •  Ciprofloxacin  : Ciprofloxacin (Systemic) may increase the serum concentration of Pirfenidone.
  •  Deferasirox  : CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone.
  •  Desogestrel  : CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone.
  •  Ethinyl Estradiol  : CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone.
  •  Ethynodiol  : CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone.
  •  Fluvoxamine  : CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pirfenidone.
  •  Gemfibrozil  : CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone.
  •  Methoxsalen  : CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pirfenidone.
  •  Nintedanib  : May decrease the serum concentration of Nintedanib.
  •  Ofloxacin  : CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pirfenidone.
  •  Phenobarbital  : CYP1A2 Inducers (Strong) may decrease the serum concentration of Pirfenidone.
  •  Primaquine  : CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pirfenidone.
  •  Primidone  : CYP1A2 Inducers (Strong) may decrease the serum concentration of Pirfenidone.
  •  Rifampicin  : CYP1A2 Inducers (Strong) may decrease the serum concentration of Pirfenidone.
  •  Stiripentol  : CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pirfenidone.
  •  Tranylcypromine  : CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone.
  •  Vemurafenib  : CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone.

Calculated Property

kind Value Source
logP 2 ALOGPS
logS -1.8 ALOGPS
Water Solubility 2.89e+00 g/l ALOGPS
logP 2.14 ChemAxon
IUPAC Name 5-methyl-1-phenyl-1,2-dihydropyridin-2-one ChemAxon
Traditional IUPAC Name pirfenidone ChemAxon
Molecular Weight 185.2218 ChemAxon
Monoisotopic Weight 185.084063979 ChemAxon
SMILES CC1=CN(C(=O)C=C1)C1=CC=CC=C1 ChemAxon
Molecular Formula C12H11NO ChemAxon
InChI InChI=1S/C12H11NO/c1-10-7-8-12(14)13(9-10)11-5-3-2-4-6-11/h2-9H,1H3 ChemAxon
InChIKey InChIKey=ISWRGOKTTBVCFA-UHFFFAOYSA-N ChemAxon
Polar Surface Area (PSA) 20.31 ChemAxon
Refractivity 57 ChemAxon
Polarizability 20.28 ChemAxon
Rotatable Bond Count 1 ChemAxon
H Bond Acceptor Count 1 ChemAxon
H Bond Donor Count 0 ChemAxon
pKa (strongest basic) -1.2 ChemAxon
Physiological Charge 0 ChemAxon
Number of Rings 2 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 1 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Furin : in Human