Exogenous surfactant kinetics in infant respiratory distress syndrome: A novel method with stable isotopes.
Little is known about surfactant metabolism in newborn infants, since radioactive isotopes cannot be used in humans. We describe here a new method for studying exogenous surfactant pharmacokinetics in vivo. We measured surfactant half-life, pool size, and turnover time in eight preterm infants (gestational age: 30 +/- 2 wk; birth weight: 1,416 +/- 202 g) who were mechanically ventilated because of infant respiratory distress syndrome. We administered two doses of 100 mg/kg each of a natural porcine surfactant with (13)C-labeled dipalmitoylphosphatidylcholine as a tracer. The (13)C enrichment of surfactant disaturated phosphatidylcholine (DSPC) was measured in serial tracheal aspirates by gas chromatography-mass spectrometry. The DSPC half-life was 34.2 +/- 9.4 h (mean +/- SD; range: 21.8 to 45.9 h). The apparent DSPC pool sizes were 5.8 +/- 6.1 mg/kg (range: 0.1 to 17.0 mg/kg) and 17.3 +/- 13.6 mg/kg (range: 3.3 to 41.0 mg/kg) at the time of the first and second surfactant doses, respectively. We present a novel and safe method that allows the tracing of exogenous surfactant phosphatidylcholine, the major lipid component of pulmonary surfactant, in infants who receive exogenous surfactant. This method could be a valuable tool for studying: (1) therapies that enhance lung/surfactant maturation; (2) the dosing and timing of surfactant therapy in different lung diseases; and (3) the comparison of different surfactant preparations.
Torresin
M
M
Department of Pediatrics, University of Padua, Padua, Italy.
Zimmermann
L J
LJ
Cogo
P E
PE
Cavicchioli
P
P
Badon
T
T
Giordano
G
G
Zacchello
F
F
Sauer
P J
PJ
Carnielli
V P
VP
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000493:pharmacokinetics; D001688:Biological Products; D002247:Carbon Isotopes; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000378:metabolism* / Q000628:therapy; D010743:Phospholipids; D011663:Pulmonary Surfactants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000378:metabolism* / Q000628:therapy; D014132:Trachea / Q000737:chemistry
D001688:Biological Products; D002247:Carbon Isotopes; D010743:Phospholipids; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine; C068291:poractant alfa