Poractant Alfa
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Poractant alfa is a
pulmonary surfactant Pulmonary surfactant is a surface-active complex of phospholipids and proteins formed by type II alveolar cells. The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic In chemistry, hydrophobicity is t ...
sold under the brand name Curosurf by Chiesi Farmaceutici. Poractant alfa is an extract of natural porcine lung surfactant. As with other surfactants, marked improvement on oxygenation may occur within minutes of the administration of poractant alfa. The new generic form of surfactant is Varasurf (Sheep Lung Surfactant) developed in PersisGen Co. and commercialized by ArnaGen Pharmad. It has fully comparable quality profile with Curosurf.


Pharmacology

Each milliliter of poractant alfa contains 80 mg of surfactant (extract) that includes 76 mg of phospholipids and 1 mg of protein of which 0.2 mg is
surfactant protein B Surfactant protein B is an essential lipid-associated protein found in pulmonary surfactant. Without it, the lung would not be able to inflate after a deep breath out. It rearranges lipid molecules in the fluid lining the lung so that tiny air sa ...
(SP-B). Depending on local country registration, CUROSURF is available in 1.5 mL vials, 3.0 mL vials, and/or twin packs containing two 1.5 mL vials. The amount of
phospholipid Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
s is calculated from the content of phosphorus and contains 55 mg of phosphatidylcholine of which 30 mg is dipalmitoylphosphatidylcholine.


Other adverse effects

Transient episodes of
bradycardia Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...
, decreased oxygen saturation,
hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...
, or
endotracheal tube A tracheal tube is a catheter that is inserted into the trachea for the primary purpose of establishing and maintaining a patent airway and to ensure the adequate exchange of oxygen and carbon dioxide. Many different types of tracheal tubes are a ...
blockage may occur.


Mechanism of action

Endogenous
pulmonary surfactant Pulmonary surfactant is a surface-active complex of phospholipids and proteins formed by type II alveolar cells. The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic In chemistry, hydrophobicity is t ...
reduces surface tension at the air-liquid interface of the alveoli during
mechanical ventilation Mechanical ventilation, assisted ventilation or intermittent mandatory ventilation (IMV), is the medical term for using a machine called a ventilator to fully or partially provide artificial ventilation. Mechanical ventilation helps move air ...
and stabilizes the
alveoli Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit. Uses in anatomy and zoology * Pulmonary alveolus, an air sac in the lungs ** Alveolar cell or pneumocyte ** Alveolar duct ** Alveolar macrophage * ...
against collapse at resting transpulmonary pressures. A deficiency of pulmonary surfactant in preterm infants results in respiratory distress syndrome. Poractant alfa compensates for the surfactant deficiency and restores surface activity to the lung tissue.


History

Surfactant deficiency was identified as the cause of respiratory distress syndrome (RDS) as long ago as 1959. Trials of surfactant replacement in the 1960s were unsuccessful because the preparations used contained only phospholipids and they were administered inefficiently by nebulization. In the 1970s Bengt Robertson and Göran Enhörning showed that natural surfactant, containing both phospholipids and proteins, could ameliorate the signs of RDS in immature rabbits. In the 1980s Bengt Robertson and Tore Curstedt developed a porcine surfactant, Curosurf (named after their surnames), which was effective in immature animals and was used in a pilot clinical trial beginning in 1983. Subsequent randomized clinical trials were planned a year later by Bengt Robertson, Tore Curstedt and Henry Halliday, and the first trial was begun in 1985. This showed that Curosurf reduced pulmonary air leaks and neonatal mortality in preterm infants with severe RDS. A second trial, coordinated by
Christian P. Speer Christian P. Speer (born 28 August 1952, in Kassel) is a German pediatrician and Professor of Pediatrics specialized in neonatology at the Julius Maximilian University of Würzburg. Speer is known for his scientific and educational contributions in ...
, demonstrated that multiple doses of Curosurf were more effective than a single dose. Subsequent trials conducted by the Collaborative European Multicenter Study Group, which included among others Guilio Bevilacqua, Janna Koppe, Ola Saugstad, Nils Svenningsen and Jean-Pierre Relier, showed that early treatment was more effective than later administration and that infants treated at birth had similar neurodevelopmental status to untreated controls at a corrected age of 2 years. Members of the Collaborative European Multicenter Study Group in Denmark and Sweden performed studies to demonstrate the benefits of a combination of surfactant treatment and early continuous positive airway pressure. As with other surfactants, marked improvements in oxygenation may occur within minutes of the administration of Curosurf.


References

{{reflist Drugs acting on the respiratory system