title: Propranolol concentrations after oral administration in term and preterm neonates.
abstract: OBJECTIVE
  While propranolol pharmacokinetics has been extensively studied in adults, this study reports the first evaluation of propranolol pharmacokinetics in term and preterm neonates.
  
  
  METHODS
  Propranolol concentrations were measured in four term and 32 preterm newborns treated with oral propranolol at the dose of 0.5 or 0.25 mg/kg every 6 h by serial dried blood spots.
  
  
  RESULTS
  The levels of propranolol, although with high inter-individual variability, were proportional with the administered dose. Pharmacokinetic parameters evaluated at the steady state in newborns treated with 0.5 mg/kg/6 h showed values of maximal (71.7 ± 29.8 ng/mL), minimal (42.2 ± 20.8 ng/mL) and average concentration (60.8 ± 25.0 ng/mL), time of maximal concentration (2.6 ± 0.9 h) and area under the time-concentration curve (364.7 ± 150.2 ng/mL/h) similar to those observed in adults. In both dosing groups, elimination half-life was significantly longer (14.9 ± 4.3 and 15.9 ± 6.1 h), and apparent total body clearance (27.2 ± 13.9 and 31.3 ± 13.3 mL/kg/min) lower than those reported in adults, suggesting a slower metabolism in newborns. No differences were observed between newborns with different gestational age or different sex.
  
  
  CONCLUSIONS
  Neonates treated with propranolol-exhibited drug concentrations proportional with the dose, with significant long half-life.
authors.affiliation: Neonatal Intensive Care Unit, Medical Surgical Feto-Neonatal Department, A. Meyer University Children's Hospital, Florence, Italy. l.filippi@meyer.it
authors.forename: L
authors.initials: L
authors.lastname: Filippi
authors.forename: G
authors.initials: G
authors.lastname: Cavallaro
authors.forename: P
authors.initials: P
authors.lastname: Fiorini
authors.forename: S
authors.initials: S
authors.lastname: Malvagia
authors.forename: M L
authors.initials: ML
authors.lastname: Della Bona
authors.forename: E
authors.initials: E
authors.lastname: Giocaliere
authors.forename: P
authors.initials: P
authors.lastname: Bagnoli
authors.forename: M
authors.initials: M
authors.lastname: Dal Monte
authors.forename: F
authors.initials: F
authors.lastname: Mosca
authors.forename: G
authors.initials: G
authors.lastname: Donzelli
authors.forename: G
authors.initials: G
authors.lastname: la Marca
mesh_terms: D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D011433:Propranolol / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000319:Adrenergic beta-Antagonists; D011433:Propranolol