Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: lung surfactant, ATC code: R07AA02.

Lung surfactant is a mixture of substances, mainly phospholipids and specific proteins, lining the internal surface of alveoli. Their main function is to lower pulmonary surface tension. This surface tension lowering activity is essential to stabilise alveoli, and to avoid collapse at end of expiration, so that adequate gas exchange is maintained throughout the ventilation cycle.
Deficiency of lung surfactant, whatever its cause, leads to severe respiratory failure which in preterm infants is known as Respiratory Distress Syndrome (RDS) or Hyaline Membrane Disease.

RDS is the principal cause of mortality and acute morbidity in preterm infants and may also be responsible for long-term respiratory and neurological sequelae. The possibility of combating this deficiency of endogenous pulmonary surfactant by the administration of supplementary surfactant directly into the lower respiratory tract is what led to the development of CUROSURF.
The surface properties of CUROSURF favour its uniform distribution in the lungs and spreading at the air-liquid interfaces in the alveoli.
The physiological and therapeutic effects of CUROSURF in surfactant deficiency have been extensively documented in various animal models.
In immature rabbit foetuses obtained by hysterectomy and immediately sacrificed before starting to breathe, the administration of CUROSURF caused a marked improvement in lung expansion.
In premature rabbits ventilated with 100% oxygen there was a dramatic improvement of tidal volume and lung-thorax compliance, compared to the control animals, after instillation of CUROSURF via a tracheal cannula.
Also in premature rabbits, maintaining a standardised tidal volume of about 10 ml/kg, treatment with CUROSURF increased lung-thorax compliance to a level similar to that of full term new-born animals.
Clinical efficacy and safety
Large international both open and controlled clinical trials have documented the therapeutic effects of CUROSURF in neonates with RDS and preterm infants at risk for RDS.
Preterm new-born infants treated with a single dose of CUROSURF (1.25-2.5 ml/kg equal to 100-200 mg/kg of phospholipids) showed a rapid and dramatic improvement of oxygenation with reduction of the inhaled oxygen concentration (FiO2) and increase of PaO2, and of PaO2/FiO2 and a/APO2 ratios; mortality rate and incidence of major pulmonary complications showed to be reduced.
The administration of a second or a third dose of 100 mg/kg seems to further reduce the incidence of pneumothorax and mortality.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties
CUROSURF remains mainly in the lungs following endotracheal administration, with a half-life of 67 14 hours of C-labelled dipalmitoyl-phosphatidylcholine in new-born rabbits.
Only traces of lipids can be found in serum and organs other than the lungs 48 hours after administration.