Uptake and degradation of Curosurf after tracheal administration to newborn and adult rabbits.
This paper examines the removal from the airways of Curosurf, a commercial surfactant derived from porcine lungs, administered at pharmacological concentrations to newborn or adult animals. Curosurf was labelled by the addition of radioactive dipalmitoyl phosphatidylcholine (DPPC) and administered intratracheally to newborn and adult rabbits at a dose of 200 mg x kg(-1) body weight. The disappearance of DPPC from the airways and its appearance in alveolar macrophages, lung parenchyma, lamellar bodies, serum, liver, kidneys and brain was then studied for 24-48 h. The in vitro degradation of Curosurf DPPC by alveolar macrophages was also studied. During the first 3 h after instillation, large amounts of Curosurf left the airways and became associated with tissue, indicating that it mixed rapidly with the endogenous pools of surfactant. A fraction of administered DPPC became associated with the lamellar bodies, suggesting that Curosurf can be recycled. Curosurf administration did not stop the secretion of endogenous surfactant. Very little intact radioactive DPPC could be recovered at any time in alveolar macrophages, however, macrophages have the ability, in vitro, to degrade Curosurf. Newborn rabbits lose Curosurf from the lungs at a slower rate than adult rabbits. One and two days after instillation, organic extracts from the liver, kidney, brain and serum contained small but measurable amounts of radioactivity. These results indicate that Curosurf rapidly enters the pathways of surfactant metabolism and that alveolar macrophages may play an important role in the catabolism of Curosurf.
Alberti
A
A
Dept of Internal Medicine, University of Padova, Italy.
Pettenazzo
A
A
Enzi
G B
GB
Palamidese
A
A
Mapp
C
C
Ventura
P
P
Baritussio
A
A
D015060:1,2-Dipalmitoylphosphatidylcholine; D000818:Animals; D000831:Animals, Newborn; D001688:Biological Products; D002250:Carbon Radioisotopes; D005260:Female; D007322:Instillation, Drug; D007442:Intubation, Intratracheal; D008168:Lung / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism*; D010743:Phospholipids; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D013997:Time Factors; D014018:Tissue Distribution
D001688:Biological Products; D002250:Carbon Radioisotopes; D010743:Phospholipids; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine; C068291:poractant alfa