title: Pharmacokinetics and clinical predictors of surfactant redosing in respiratory distress syndrome.
abstract: BACKGROUND
  Limited data are available on predictors for surfactant retreatment in preterm infants with respiratory distress syndrome (RDS).
  
  
  OBJECTIVE
  To study the pharmacokinetics of exogenous surfactant and the clinical parameters associated with surfactant redosing.
  
  
  METHODS
  Exogenous surfactant pharmacokinetics was studied in 125 preterm infants (birth weight 997 ± 432 g; gestational age 28.0 ± 2.6 weeks) with moderate to severe RDS requiring mechanical ventilation. Clinical and respiratory parameters were recorded hourly, and surfactant disaturated-phosphatidylcholine (DSPC) half-life, pool size, and endogenous synthesis were calculated by stable isotope tracing of surfactant DSPC isolated from serial tracheal aspirates. Univariate and multiple logistic regression were used to study the effects of clinical and surfactant kinetic variables on the need for redosing.
  
  
  RESULTS
  Fifty-three infants (42.4%) received one dose, 51 (40.8%) two doses, and 21 (16.8%) three doses. Median (interquartile range, IQR) DSPC half-life was 21 (13-39), 11 (7-17), and 10 (7-16) h after the first, second, and third dose, respectively (p = 0.07). Univariate analysis showed a significantly shorter DSPC half-life in infants requiring more surfactant doses. On logistic analysis, risk of redosing was higher with lower birth weight, worse radiological score, shorter DSPC half-life, and surfactant dose of 100 mg/kg, whilst it was lower with elective high-frequency ventilation at time of intubation, instead of conventional ventilation.
  
  
  CONCLUSIONS
  When optimizing surfactant replacement therapy and its cost-benefit ratio, pharmacokinetics and clinical variables associated with need of redosing should be taken into account.
authors.affiliation: Department of Paediatrics, University of Padova, Padova, Italy. cogo@pediatria.unipd.it
authors.forename: Paola E
authors.initials: PE
authors.lastname: Cogo
authors.forename: Maddalena
authors.initials: M
authors.lastname: Facco
authors.forename: Manuela
authors.initials: M
authors.lastname: Simonato
authors.forename: Daniele
authors.initials: D
authors.lastname: De Luca
authors.forename: Francesca
authors.initials: F
authors.lastname: De Terlizi
authors.forename: Umberto
authors.initials: U
authors.lastname: Rizzotti
authors.forename: Giovanna
authors.initials: G
authors.lastname: Verlato
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Bellagamba
authors.forename: Virgilio P
authors.initials: VP
authors.lastname: Carnielli
mesh_terms: D005260:Female; D005544:Forecasting; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007553:Isotope Labeling / Q000379:methods; D007558:Italy; D016015:Logistic Models; D008297:Male; D010713:Phosphatidylcholines / Q000032:analysis; D011446:Prospective Studies; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy*; D019233:Retreatment; D013501:Surface-Active Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D010713:Phosphatidylcholines; D013501:Surface-Active Agents