title: Inhalable powder formulation of pirfenidone with reduced phototoxic risk for treatment of pulmonary fibrosis.
abstract: OBJECTIVE
  Orally-taken pirfenidone (PFD), an idiopathic pulmonary fibrosis drug, often causes severe phototoxicity. Present study aimed to develop a respirable powder formulation for PFD (PFD-RP) to minimize phototoxic risk.
  
  
  METHODS
  Photochemical properties of PFD were examined using a reactive oxygen species (ROS) assay and photostability testing. PFD-RP was characterized with a focus on photostability, in vitro inhalation performance, and the efficacy in antigen-sensitized rats. Pharmacokinetic studies were conducted after oral and intratracheal administration of PFD formulations.
  
  
  RESULTS
  Although PFD solution exhibited photodegradation under simulated sunlight (250 W/m²), both PFD powder and PFD-RP were photochemically stable. Laser diffraction and cascade impactor analyses on PFD-RP suggested its high dispersion and fine in vitro inhalation performance. Inhaled PFD-RP (300 μg-PFD/rat) could suppress antigen-evoked pulmonary inflammation in rats as evidenced by decreases in recruited inflammatory cells and neutrophilia-related biomarkers in the lung. Exposure of PFD to light-exposed tissues (skin and eye) after intratracheal administration of PFD-RP at a pharmacologically effective dose (300 μg-PFD/rat) was 90-130-fold less than that of the oral PFD dosage form at a phototoxic dose (160 mg/kg).
  
  
  CONCLUSIONS
  PFD-RP might be an attractive alternative to the current oral PFD therapy with a better safety margin.
authors: Department of Pharmacokinetics and Pharmacodynamics School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. onoue@u-shizuoka-ken.ac.jp
authors: Satomi
authors: S
authors: Onoue
authors: Yoshiki
authors: Y
authors: Seto
authors: Masashi
authors: M
authors: Kato
authors: Yosuke
authors: Y
authors: Aoki
authors: Yoshiki
authors: Y
authors: Kojo
authors: Shizuo
authors: S
authors: Yamada
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D017484:Dermatitis, Phototoxic / Q000517:prevention & control*; D008168:Lung / Q000187:drug effects; D008297:Male; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000737:chemistry; D011014:Pneumonia / Q000188:drug therapy; D011208:Powders / Q000008:administration & dosage / Q000737:chemistry; D011658:Pulmonary Fibrosis / Q000188:drug therapy*; D011728:Pyridones / Q000008:administration & dosage* / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D019999:Pharmaceutical Solutions; D011208:Powders; D011728:Pyridones; C093844:pirfenidone