Pirfenidone

From Wikipedia, the free encyclopedia

Pirfenidone
Clinical data
Trade namesEsbriet, Pirespa, Etuary
AHFS/Drugs.comMonograph
MedlinePlusa615008
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding50–58%[7]
MetabolismLiver (70–80% CYP1A2-mediated; minor contributions from CYP2C9, CYP2C19, CYP2D6 and CYP2E1)[7]
Elimination half-life2.4 hours[7]
ExcretionUrine (80%)[7]
Identifiers
  • 5-Methyl-1-phenylpyridin-2-one
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.150.129 Edit this at Wikidata
Chemical and physical data
FormulaC12H11NO
Molar mass185.226 g·mol−1
3D model (JSmol)
Solubility in water10mg/mL at 60 °C
  • CC1=CN(C(=O)C=C1)C2=CC=CC=C2
  • InChI=1S/C12H11NO/c1-10-7-8-12(14)13(9-10)11-5-3-2-4-6-11/h2-9H,1H3
  • Key:ISWRGOKTTBVCFA-UHFFFAOYSA-N
 ☒NcheckY (what is this?)  (verify)

Pirfenidone, sold under the brand name Pirespa among others, is a medication used for the treatment of idiopathic pulmonary fibrosis. It works by reducing lung fibrosis through downregulation of the production of growth factors and procollagens I and II.

It was first approved in Japan for the treatment of people with idiopathic pulmonary fibrosis after clinical trials in 2008. It was approved for use in the European Union in 2011,[8][6] in Canada in 2012,[4] and in the United States in October 2014.[5][9]

It is available as a generic medication.[10]

Medical uses[edit]

In the European Union, pirfenidone is indicated for the treatment of mild-to-moderate idiopathic pulmonary fibrosis. It was approved by the European Medicines Agency in 2011.[8][6] In October 2008, it was approved for use in Japan, in India in 2010, and in China in 2011 (commercial launch in 2014). In October 2014, it was approved for medical use in the United States.[5][9] A tablet version was approved for use in the United States in January 2017.[5][11]

In Mexico it was approved as a gel[12] for the treatment of scars and fibrotic tissue.[13]

Adverse effects[edit]

Gastrointestinal[edit]

Pirfenidone is frequently associated with gastrointestinal side effects such as dyspepsia, nausea, gastritis, gastroesophageal reflux disease and vomiting. To reduce the severity of these reactions, pirfenidone is to be taken after meals.[14]

Skin[edit]

Pirfenidone is known to cause photosensitivity reactions, rash, pruritus and dry skin. Patients are usually advised to avoid direct exposure to sunlight, including sun lamps, and to use protective clothing and sunscreening agents. Continuing photosensitivity reactions are usually managed by dose adjustment and temporary discontinuation of treatment if required, along with local symptomatic treatment.[14]

Hepatic dysfunction[edit]

Pirfenidone can increase hepatic enzyme levels, especially those of aspartate transaminase, alanine transaminase and gamma-glutamyl transpeptidase; periodic monitoring of hepatic enzyme levels is required during therapy: once before the initiation of therapy, monthly monitoring until 6 months after initiation of therapy, and 3 monthly thereafter. Extra precaution is required while prescribing the drug in patients with hepatic impairment and in patients who are concomitantly taking a CYP1A2 inhibitor. The drug is contraindicated in patients who have severe hepatic impairment.[14]

Dizziness and fatigue[edit]

Dizziness and fatigue have been reported in patients undergoing pirfenidone treatment. Dizziness typically resolves, although patients should know how they react to pirfenidone before undertaking activities that need mental alertness or coordination. If severe, dose adjustment or treatment discontinuation may be required.[14]

Weight loss[edit]

Weight loss has been reported in patients treated with pirfenidone. Doctors should monitor patients’ weight and encourage increased caloric intake if necessary.[14]

Interactions[edit]

Most drug interactions are mediated by various cytochrome P450 enzymes.[14]

CYP1A2 inhibitors[edit]

Since Pirfenidone is metabolised through the CYP1A2 enzyme pathway, any drug which inhibits this enzyme is likely to precipitate the toxicity of pirfenidone: concomitant therapy is to be avoided. Fluvoxamine is contraindicated in patients who are on treatment with pirfenidone. Other inhibitors of CYP1A2 such as ciprofloxacin, amiodarone and propafenone should be used with caution.[14]

Other CYP inhibitors[edit]

Some pirfenidone is also metabolized by cytochrome P450 enzymes other than CYP1A2. Consequently, strong inhibitors of other cytochrome P450 enzymes such as fluconazole (CYP2C9), chloramphenicol (CYP2C19), fluoxetine and paroxetine (both CYP2D6) should be used with caution.[14]

CYP1A2 inducers[edit]

Moderate inducers of CYP1A2 such as omeprazole should be used with caution since they might reduce the circulating plasma levels of the drug.[14]

Cigarette smoking[edit]

Cigarette smoking causes increased clearance of pirfenidone by inducing CYP1A2, thereby decreasing exposure to the drug. Patients must be advised to abstain from cigarette smoking while on therapy with pirfenidone.[14]

Pharmacology[edit]

Mechanism of action[edit]

Pirfenidone has well-established antifibrotic and anti-inflammatory properties in various in vitro systems and animal models of fibrosis.[15] A number of cell-based studies have shown that pirfenidone reduces fibroblast proliferation,[16][17][18][19] inhibits transforming growth factor beta stimulated collagen production[16][17][20][21][22] and reduces the production of fibrogenic mediators such as transforming growth factor beta.[18][21] Pirfenidone has also been shown to reduce production of inflammatory mediators such as tumor necrosis factor alpha and IL-1β in both cultured cells and isolated human peripheral blood mononuclear cells.[23][24] These activities are consistent with the broader antifibrotic and anti-inflammatory activities observed in animal models of fibrosis.[citation needed]

Pharmacokinetics[edit]

Pirfenidone is administered orally. Though the presence of food significantly reduces the extent of absorption, the drug is to be taken after food, to reduce the nausea and dizziness associated with the drug. The drug is around 60% bound to plasma proteins, especially to albumin.[14] Up to 50% of the drug is metabolized by hepatic CYP1A2 enzyme system to yield 5-carboxypirfenidone, the inactive metabolite. Almost 80% of the administered dose is excreted in the urine within 24 hours of intake.[14]

History[edit]

The drug was developed by several companies worldwide, including the original patent holder, Marnac,[25] InterMune (now part of Roche), Shionogi, and GNI Group.

In August 2023, Roche subsidiary Genentech sued Novartis in a New Jersey court. The lawsuit asserts that Novartis subsidiary Sandoz did not apply for a license when it began to sell pirfenidone in the U.S. market. Esbriet had a revenue of $740 million in the U.S. market (2021), and Genentech alleges that Sandoz's unlawful sale of pirfenidone has caused "significant financial harm."[26]

Preclinical studies in models of fibrosis[edit]

In animal models, pirfenidone displays a systemic antifibrotic activity and has been shown to reduce biochemical and histopathological indices of fibrosis of the lung, liver, heart and kidney.[15]

Pirfenidone demonstrates a consistent antifibrotic effect in several animal models of pulmonary fibrosis.[27][28][29][30][31] Of these, the bleomycin model is the most widely used model of pulmonary fibrosis. In this model, bleomycin administration results in oxidative stress and acute inflammation, with the subsequent onset of pulmonary fibrosis in a number of animal species including the mouse and hamster.[15][29] Numerous studies have demonstrated that pirfenidone attenuates bleomycin-induced pulmonary fibrosis.[27][28][31][32][33][34] One study investigated the effect of pirfenidone over a 42-day period after repeated bleomycin administration.[28] Administration of pirfenidone minimised early lung oedema and pulmonary fibrosis when treatment was initiated concurrently with lung damage. This study evaluated pulmonary protein expression and found pirfenidone treatment normalised expression of proinflammatory and fibrogenic proteins. Similar reductions in pulmonary fibrosis were observed when pirfenidone treatment was delayed until pulmonary fibrosis was established and progressing,[27] i.e. when administered in a therapeutic as opposed to a prophylactic treatment regimen.

The antifibrotic effect of pirfenidone has been further established in animal models of cardiac (heart),[35][36][37] renal (kidney),[38][39] and hepatic (liver)[16][40][41] fibrosis, as well as in Dupuytren's contracture.[42] In these models, pirfenidone demonstrated a consistent ability to reduce fibrosis and the expression of fibrogenic mediators.[citation needed]

Pirfenidone has also been shown to inhibit spondyloarthritis fibroblast-like synoviocytes and osteoblasts in vitro.[43]

Clinical trials in idiopathic pulmonary fibrosis[edit]

The clinical efficacy of pirfenidone has been studied in three Phase III, randomized, double-blind, placebo-controlled studies in patients with idiopathic pulmonary fibrosis.[44][45]

The first Phase III clinical trial to evaluate the efficacy and safety of pirfenidone for the treatment of patients with idiopathic pulmonary fibrosis was conducted in Japan. This was a multicentre, randomised, double-blind, trial, in which 275 patients with idiopathic pulmonary fibrosis were randomly assigned to receive pirfenidone 1800 mg/day (110 patients), pirfenidone 1200 mg/day (56 patients), or placebo (109 patients), for 52 weeks. Pirfenidone 1800 or 1200 mg/day reduced the mean decline in vital capacity from baseline to week 52 compared with placebo. Progression-free survival was also improved with pirfenidone compared with placebo.[44]

Two randomized, double-blind, placebo-controlled Phase III studies in eleven countries across Europe, North America, and Australia.[45] Patients with idiopathic pulmonary fibrosis were randomly assigned to treatment with oral pirfenidone or placebo for a minimum of 72 weeks.[45] In study 004, pirfenidone reduced decline in forced vital capacity. Mean change in FVC at week 72 was –8.0% in the pirfenidone 2403 mg/day group and –12.4% in the placebo group, a difference of 4.4%. Thirty-five (20%) of 174 versus 60 (35%) of 174 patients, respectively, had a decline in forced vital capacity of at least 10%. In study 006, the difference between groups in forced vital capaticy change at week 72 was not statistically significant. Mean change in forced vital capacity FVC at week 72 was –9.0% in the pirfenidone group and –9.6% in the placebo group. The difference between groups in change in predicted forced vital capacity at week 72 was not significant.[45]

In May 2014, the results of another randomized, double-blind, placebo-controlled trial that enrolled 555 patients were published. They confirmed observations from previous clinical studies that pirfenidone significantly reduced the progression of idiopathic pulmonary fibrosis as measured by change in percent predicted forced vital capacity from baseline to week 52. In addition, significant treatment effects were shown on both of the key secondary endpoints of six-minute walk test distance change and progression-free survival. A pre-specified analysis of the pooled population of 1,247 subjects from three studies showed that the risk of all-cause mortality was reduced by 48% in the pirfenidone group compared to the placebo group.[46]

A review by the Cochrane Collaboration concluded that pirfenidone appears to improve progression-free survival and, to a lesser effect, pulmonary function in patients with idiopathic pulmonary fibrosis.[47] Randomised studies comparing non-steroid drugs with placebo or steroids in adult patients with idiopathic pulmonary fibrosis were included. Four placebo-controlled trials of pirfenidone treatment were reviewed, involving a total of 1155 patients. The result of the meta-analysis showed that pirfenidone significantly reduces the risk of disease progression by 30%. In addition, meta-analysis of the two Japanese studies confirmed the beneficial effect of pirfenidone on the change in vital capacity from baseline compared with placebo.[47]

Regulatory progress[edit]

In May 2010, the U.S. Food and Drug Administration (FDA) declined to approve the use of pirfenidone for the treatment of idiopathic pulmonary fibrosis, requesting additional clinical trials.[48] In December 2010, an advisory panel to the European Medicines Agency (EMA) recommended approval of the drug.[8] In February 2011, the European Commission granted marketing authorisation in all 27 EU member states and the China Food and Drug Administration granted approval in September 2011. Afterwards, a randomised, Phase III trial was completed in the U.S. in 2014,[49] with regulatory approval in U.S. following shortly after.

In October 2010, the Indian Company Cipla launched the drug as Pirfenex, and MSN laboratories launched it as Pulmofib. It was approved for use in the European Union in 2011, under the brand name Esbriet;[8] it was approved in Canada in 2012 under the same name; and was approved in the United States in October 2014, also as Esbriet. In September 2011, the Chinese State Food and Drug Administration provided GNI Group Ltd with new drug approval of pirfenidone in China,[50] and later manufacture approval in 2013, under the brand name of Etuary.[51]

In 2014, it was approved in Mexico under the name KitosCell LP, indicated for pulmonary fibrosis and liver fibrosis.[52] In Mexico it has also been approved in gel for the treatment of chronic wounds and skin injuries and the oral form it is approved for the treatment of pulmonary fibrosis and liver fibrosis.[citation needed]

Research[edit]

Other research shows that pirfenidone may be an effective anti-fibrotic treatment[53] for chronic liver fibrosis.[54]

References[edit]

  1. ^ a b "Archived copy". Archived from the original on 8 January 2023. Retrieved 8 January 2023.{{cite web}}: CS1 maint: archived copy as title (link)
  2. ^ "Archived copy". Archived from the original on 8 January 2023. Retrieved 8 January 2023.{{cite web}}: CS1 maint: archived copy as title (link)
  3. ^ "Prescription medicines: registration of new chemical entities in Australia, 2016". Therapeutic Goods Administration (TGA). 21 June 2022. Archived from the original on 10 April 2023. Retrieved 10 April 2023.
  4. ^ a b "Esbriet Product information". Health Canada. 25 April 2012. Archived from the original on 8 January 2023. Retrieved 8 January 2023.
  5. ^ a b c d "Esbriet- pirfenidone capsule Esbriet- pirfenidone tablet, coated". DailyMed. 14 December 2022. Archived from the original on 8 January 2023. Retrieved 8 January 2023.
  6. ^ a b c "Esbriet EPAR". European Medicines Agency. 17 September 2018. Archived from the original on 24 November 2020. Retrieved 19 June 2020.
  7. ^ a b c d "Esbriet 267 mg hard capsules". electronic Medicines Compendium. Intermune UK & I Ltd. 3 January 2014. Archived from the original on 12 October 2013. Retrieved 6 March 2014.
  8. ^ a b c d "InterMune: Pirfenidone". InterMune. Archived from the original on 21 October 2020. Retrieved 17 December 2015.
  9. ^ a b "Drug Approval Package: Esbriet (pirfenidone) Capsules NDA #022535". U.S. Food and Drug Administration. 24 December 1999. Archived from the original on 3 January 2021. Retrieved 19 June 2020.
  10. ^ "2022 First Generic Drug Approvals". U.S. Food and Drug Administration (FDA). 3 March 2023. Archived from the original on 30 June 2023. Retrieved 30 June 2023.
  11. ^ "Esbriet (pirfenidone) Film-coated Tablets". U.S. Food and Drug Administration. 21 February 2018. Archived from the original on 22 May 2020. Retrieved 19 June 2020.
  12. ^ ".::KitosCell Gel, Primer Biomodulador::". www.kitoscell.com. Archived from the original on 2 May 2021. Retrieved 18 June 2014.
  13. ^ A controlled clinical trial with pirfenidone in the treatment of pathological skin scarring caused by burns in pediatric patients, annals of plastic surgery, volume 68, number 1, January 2012
  14. ^ a b c d e f g h i j k l "Esbriet 267 mg hard capsules" (PDF). Summary of product characteristics. European Medicines Agency. Archived (PDF) from the original on 18 March 2018. Retrieved 9 March 2012.
  15. ^ a b c Schaefer CJ, Ruhrmund DW, Pan L, Seiwert SD, Kossen K (June 2011). "Antifibrotic activities of pirfenidone in animal models". European Respiratory Review. 20 (120): 85–97. doi:10.1183/09059180.00001111. PMC 9487788. PMID 21632796.
  16. ^ a b c Di Sario A, Bendia E, Svegliati Baroni G, Ridolfi F, Casini A, Ceni E, Saccomanno S, Marzioni M, Trozzi L, Sterpetti P, Taffetani S, Benedetti A (November 2002). "Effect of pirfenidone on rat hepatic stellate cell proliferation and collagen production". Journal of Hepatology. 37 (5): 584–91. doi:10.1016/S0168-8278(02)00245-3. PMID 12399223.
  17. ^ a b Hewitson TD, Kelynack KJ, Tait MG, Martic M, Jones CL, Margolin SB, Becker GJ (2001). "Pirfenidone reduces in vitro rat renal fibroblast activation and mitogenesis". Journal of Nephrology. 14 (6): 453–60. PMID 11783601.
  18. ^ a b Lin X, Yu M, Wu K, Yuan H, Zhong H (August 2009). "Effects of pirfenidone on proliferation, migration, and collagen contraction of human Tenon's fibroblasts in vitro". Investigative Ophthalmology and Visual Science. 50 (8): 3763–70. doi:10.1167/iovs.08-2815. PMID 19264889.
  19. ^ Lee BS, Margolin SB, Nowak RA (January 1998). "Pirfenidone: a novel pharmacological agent that inhibits leiomyoma cell proliferation and collagen production". Journal of Clinical Endocrinology and Metabolism. 83 (1): 219–23. doi:10.1210/jcem.83.1.4503. PMID 9435445.
  20. ^ Ozes ON, Blatt LM (2006). "Development of a high throughput collagen assay using a cellular model of idiopathic pulmonary fibrosis". Chest. 130 (4): 230S. doi:10.1378/chest.130.4_meetingabstracts.230s-a.
  21. ^ a b Sulfab M (2007). "The effects of pirfenidone and IFN-inducible T-cell alpha chemoattractant (ITAC) on transforming-growth factor-beta 1-mediated synthesis of extracellular matrix proteins in endothelial cells". American Journal of Respiratory and Critical Care Medicine. 175: A730.
  22. ^ Nakayama S, Mukae H, Sakamoto N, Kakugawa T, Yoshioka S, Soda H, Oku H, Urata Y, Kondo T, Kubota H, Nagata K, Kohno S (January 2008). "Pirfenidone inhibits the expression of HSP47 in TGF-beta1-stimulated human lung fibroblasts". Life Science. 82 (3–4): 210–7. doi:10.1016/j.lfs.2007.11.003. PMID 18093617.
  23. ^ Phillips R, Wang T, Blatt LM, Seiwert S (2005). "Pirfenidone mediates differential effects on lipopolysaccharide-induced cytokine expression in human peripheral mononuclear cells". Chest. 128 (4): 169S. doi:10.1378/chest.128.4_meetingabstracts.169s-a. Archived from the original on 3 March 2016. Retrieved 16 March 2013.
  24. ^ Grattendick KJ, Nakashima JM, Feng L, Giri SN, Margolin SB (May 2008). "Effects of three anti-TNF-alpha drugs: etanercept, infliximab and pirfenidone on release of TNF-alpha in medium and TNF-alpha associated with the cell in vitro". International Immunopharmacology. 8 (5): 679–87. doi:10.1016/j.intimp.2008.01.013. PMID 18387510.
  25. ^ "InterMune Buys out License Agreement for Pirfenidone". Patent Docs. Archived from the original on 14 May 2019. Retrieved 2 November 2016.
  26. ^ "Swiss pharma giants Roche and Novartis fight over patent in US court". Swissinfo. 2 August 2023. Retrieved 3 August 2023.
  27. ^ a b c Kakugawa T, Mukae H, Hayashi T, Ishii H, Abe K, Fujii T, Oku H, Miyazaki M, Kadota J, Kohno S (July 2004). "Pirfenidone attenuates expression of HSP47 in murine bleomycin-induced pulmonary fibrosis". European Respiratory Journal. 24 (1): 57–65. doi:10.1183/09031936.04.00120803. PMID 15293605.
  28. ^ a b c Oku H, Shimizu T, Kawabata T, Nagira M, Hikita I, Ueyama A, Matsushima S, Torii M, Arimura A (August 2008). "Antifibrotic action of pirfenidone and prednisolone: different effects on pulmonary cytokines and growth factors in bleomycin-induced murine pulmonary fibrosis". European Journal of Pharmacology. 590 (1–3): 400–8. doi:10.1016/j.ejphar.2008.06.046. PMID 18598692.
  29. ^ a b Card JW, Racz WJ, Brien JF, Margolin SB, Massey TE (September 2003). "Differential effects of pirfenidone on acute pulmonary injury and ensuing fibrosis in the hamster model of amiodarone-induced pulmonary toxicity". Toxicological Sciences. 75 (1): 169–80. doi:10.1093/toxsci/kfg167. PMID 12832656.
  30. ^ Liu H, Drew P, Gaugler AC, Cheng Y, Visner GA (June 2005). "Pirfenidone inhibits lung allograft fibrosis through L-arginine-arginase pathway". Am. J. Transplant. 5 (6): 1256–63. doi:10.1111/j.1600-6143.2005.00876.x. PMID 15888029. S2CID 24236706.
  31. ^ a b Hirano A, Kanehiro A, Ono K, Ito W, Yoshida A, Okada C, Nakashima H, Tanimoto Y, Kataoka M, Gelfand EW, Tanimoto M (September 2006). "Pirfenidone modulates airway responsiveness, inflammation, and remodeling after repeated challenge". American Journal of Respiratory Cell and Molecular Biology. 35 (3): 366–77. doi:10.1165/rcmb.2005-0452OC. PMC 2643289. PMID 16675785.
  32. ^ Iyer SN, Wild JS, Schiedt MJ, Hyde DM, Margolin SB, Giri SN (June 1995). "Dietary intake of pirfenidone ameliorates bleomycin-induced lung fibrosis in hamsters". Journal of Laboratory and Clinical Medicine. 125 (6): 779–85. PMID 7539478.
  33. ^ Iyer SN, Margolin SB, Hyde DM, Giri SN (1998). "Lung fibrosis is ameliorated by pirfenidone fed in diet after the second dose in a three-dose bleomycin-hamster model". Experimental Lung Research. 24 (1): 119–32. doi:10.3109/01902149809046058. PMID 9457473.
  34. ^ Iyer SN, Gurujeyalakshmi G, Giri SN (April 1999). "Effects of pirfenidone on procollagen gene expression at the transcriptional level in bleomycin hamster model of lung fibrosis". Journal of Pharmacology and Experimental Therapeutics. 289 (1): 211–8. PMID 10087006.
  35. ^ Lee KW, Everett TH, Rahmutula D, Guerra JM, Wilson E, Ding C, Olgin JE (October 2006). "Pirfenidone prevents the development of a vulnerable substrate for atrial fibrillation in a canine model of heart failure". Circulation. 114 (16): 1703–12. doi:10.1161/CIRCULATIONAHA.106.624320. PMC 2129103. PMID 17030685.
  36. ^ Nguyen DT, Ding C, Wilson E, Marcus GM, Olgin JE (October 2010). "Pirfenidone mitigates left ventricular fibrosis and dysfunction after myocardial infarction and reduces arrhythmias". Heart Rhythm. 7 (10): 1438–45. doi:10.1016/j.hrthm.2010.04.030. PMID 20433946.
  37. ^ Mirkovic S, Seymour AM, Fenning A, Strachan A, Margolin SB, Taylor SM, Brown L (February 2002). "Attenuation of cardiac fibrosis by pirfenidone and amiloride in DOCA-salt hypertensive rats". British Journal of Pharmacology. 135 (4): 961–8. doi:10.1038/sj.bjp.0704539. PMC 1573203. PMID 11861324.
  38. ^ Shimizu T, Kuroda T, Hata S, Fukagawa M, Margolin SB, Kurokawa K (July 1998). "Pirfenidone improves renal function and fibrosis in the post-obstructed kidney". Kidney International. 54 (1): 99–109. doi:10.1046/j.1523-1755.1998.00962.x. PMID 9648068.
  39. ^ Takakuta K, Fujimori A, Chikanishi T, Tanokura A, Iwatsuki Y, Yamamoto M, Nakajima H, Okada M, Itoh H (March 2010). "Renoprotective properties of pirfenidone in subtotally nephrectomized rats". European Journal of Pharmacology. 629 (1–3): 118–24. doi:10.1016/j.ejphar.2009.12.011. PMID 20006961.
  40. ^ Salazar-Montes A, Ruiz-Corro L, López-Reyes A, Castrejón-Gómez E, Armendáriz-Borunda J (October 2008). "Potent antioxidant role of pirfenidone in experimental cirrhosis". European Journal of Pharmacology. 595 (1–3): 69–77. doi:10.1016/j.ejphar.2008.06.110. PMID 18652820.
  41. ^ García L, Hernández I, Sandoval A, Salazar A, Garcia J, Vera J, Grijalva G, Muriel P, Margolin S, Armendariz-Borunda J (December 2002). "Pirfenidone effectively reverses experimental liver fibrosis". Journal of Hepatology. 37 (6): 797–805. doi:10.1016/S0168-8278(02)00272-6. PMID 12445421.
  42. ^ Zhou C, Liu F, Gallo PH, Baratz ME, Kathju S, Satish L (November 2016). "Anti-fibrotic action of pirfenidone in Dupuytren's disease-derived fibroblasts". BMC Musculoskeletal Disorders. 17 (1): 469. doi:10.1186/s12891-016-1326-y. PMC 5106805. PMID 27835939.
  43. ^ Stougaard J, Lomholt S, Ommen P, Kelsen J, Kragstrup TW. The antifibrotic drug pirfenidone inhibits spondyloarthritis fibroblast-like synoviocytes and osteoblasts in vitro Archived 20 October 2021 at the Wayback Machine. BMC Rheumatol. 2018;2:33. Published 2018 Nov 19. doi:10.1186/s41927-018-0040-9
  44. ^ a b Taniguchi H, Ebina M, Kondoh Y, et al. (April 2010). "Pirfenidone in idiopathic pulmonary fibrosis". European Respiratory Journal. 35 (4): 821–9. doi:10.1183/09031936.00005209. PMID 19996196.
  45. ^ a b c d Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, King TE, Lancaster L, Sahn SA, Szwarcberg J, Valeyre D, du Bois RM (May 2011). "Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials". Lancet. 377 (9779): 1760–9. doi:10.1016/S0140-6736(11)60405-4. PMID 21571362. S2CID 10119356.
  46. ^ "Genentech: Esbriet® (pirfenidone) - Information for Patients". Archived from the original on 13 February 2014.
  47. ^ a b Spagnolo P, Del Giovane C, Luppi F, Cerri S, Balduzzi S, Walters EH, D'Amico R, Richeldi L (2010). "Non-steroid agents for idiopathic pulmonary fibrosis". Cochrane Database of Systematic Reviews (9): CD003134. doi:10.1002/14651858.CD003134.pub2. PMID 20824834.
  48. ^ Frieden J (10 May 2010). "FDA Nixes Pirfenidone for Now, Wants New Trial". MedPage Today. Archived from the original on 17 January 2021. Retrieved 9 March 2012.
  49. ^ "Efficacy and Safety of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis (IPF)". Nct01366209. U.S. National Institutes of Health: ClinicalTrials.gov. 8 March 2017. Archived from the original on 30 January 2016. Retrieved 9 March 2012.
  50. ^ "China SFDA Approves F647/pirfenidone for the Treatment of Idiopathic Pulmonary Fibrosis". Press Release. EvaluatePharma. 22 September 2011. Archived from the original on 14 December 2019. Retrieved 9 March 2012.
  51. ^ "GNI Group receives manufacture approval for F647 from China FDA for first idiopathic pulmonary fibrosis drug in China" (PDF). Press Release. 6 January 2014. Archived from the original (PDF) on 4 March 2016. Retrieved 8 July 2014.
  52. ^ kitoscell.com
  53. ^ Macías-Barragán J, Sandoval-Rodríguez A, Navarro-Partida J, Armendáriz-Borunda J (September 2010). "The multifaceted role of pirfenidone and its novel targets". Fibrogenesis & Tissue Repair. 3: 16. doi:10.1186/1755-1536-3-16. PMC 2944211. PMID 20809935.
  54. ^ García L, Hernández I, Sandoval A, Salazar A, Garcia J, Vera J, et al. (December 2002). "Pirfenidone effectively reverses experimental liver fibrosis". Journal of Hepatology. 37 (6): 797–805. doi:10.1016/s0168-8278(02)00272-6. PMID 12445421.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Pirfenidone&oldid=1190946027"