In vitro and in vivo comparison between poractant alfa and the new generation synthetic surfactant CHF5633

Pediatr Res. 2017 Feb;81(2):369-375. doi: 10.1038/pr.2016.231. Epub 2016 Nov 3.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biological Products / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Female
  • Infant, Premature
  • Lung / drug effects
  • Peptide Fragments / therapeutic use*
  • Phosphatidylcholines / therapeutic use*
  • Phospholipids / therapeutic use*
  • Pregnancy
  • Pregnancy, Animal
  • Pulmonary Surfactant-Associated Protein B / blood
  • Pulmonary Surfactant-Associated Protein B / therapeutic use*
  • Pulmonary Surfactant-Associated Protein C / blood
  • Pulmonary Surfactant-Associated Protein C / therapeutic use*
  • Pulmonary Surfactants / therapeutic use
  • Rabbits
  • Respiration, Artificial
  • Respiratory Distress Syndrome, Newborn / drug therapy
  • Surface Tension
  • Surface-Active Agents / therapeutic use*
  • Swine

Substances

  • Biological Products
  • CHF5633
  • Peptide Fragments
  • Phosphatidylcholines
  • Phospholipids
  • Pulmonary Surfactant-Associated Protein B
  • Pulmonary Surfactant-Associated Protein C
  • Pulmonary Surfactants
  • Surface-Active Agents
  • poractant alfa