title: In vitro and in vivo comparison between poractant alfa and the new generation synthetic surfactant CHF5633.
abstract: CHF5633 is a new generation synthetic surfactant containing both SP-B and SP-C analogues developed for the treatment of respiratory distress syndrome. Here, the optimal dose and its performance in comparison to the animal-derived surfactant poractant alfa were investigated.
  
  
  
  In vitro surfactant activity was determined by means of the Wilhelmy balance and the capillary surfactometer. The dose-finding study was performed in preterm rabbits with severe surfactant deficiency. CHF5633 doses ranging from 50 to 300 mg/kg were used. Untreated animals and animals treated with 200 mg/kg of poractant alfa were included for comparison.
  
  
  
  In vitro, minimum surface tension (γmin) was decreased from values above 70 to 0 mN/m by both surfactants, and they formed rapidly a film at the air-liquid interface. In vivo studies showed a clear dose-dependent improvement of lung function for CHF5633. The pulmonary effect of CHF5633 200 mg/kg dose was comparable to the pulmonary response elicited by 200 mg/kg of poractant alfa in preterm rabbits.
  
  
  
  CHF5633 is as efficient as poractant alfa in our in vitro and in vivo settings. A clear dose-dependent improvement of lung function could be observed for CHF5633, with the dose of 200 mg/kg being the most efficient one.
authors.affiliation: R&D Department, Chiesi Farmaceutici, Parma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ricci
authors.affiliation: Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany.
authors.forename: Xabier
authors.initials: X
authors.lastname: Murgia
authors.affiliation: R&D Department, Chiesi Farmaceutici, Parma, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Razzetti
authors.affiliation: R&D Department, Chiesi Farmaceutici, Parma, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Pelizzi
authors.affiliation: R&D Department, Chiesi Farmaceutici, Parma, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Salomone
mesh_terms: D000818:Animals; D005260:Female; D011247:Pregnancy; D011817:Rabbits; D000831:Animals, Newborn; D001688:Biological Products / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008168:Lung / Q000187:drug effects; D010446:Peptide Fragments / Q000627:therapeutic use; D010713:Phosphatidylcholines / Q000627:therapeutic use; D010743:Phospholipids / Q000627:therapeutic use; D011270:Pregnancy, Animal; D037701:Pulmonary Surfactant-Associated Protein B / Q000097:blood / Q000627:therapeutic use; D037721:Pulmonary Surfactant-Associated Protein C / Q000097:blood / Q000627:therapeutic use; D011663:Pulmonary Surfactants / Q000627:therapeutic use; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy; D013500:Surface Tension; D013501:Surface-Active Agents / Q000627:therapeutic use; D013552:Swine
chemical_list: D001688:Biological Products; C000592408:CHF5633; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010743:Phospholipids; C068291:poractant alfa; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; D013501:Surface-Active Agents