title: Longitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants: pharmacokinetics and short-term safety.
abstract: BACKGROUND
  In preterm infants, low levels of insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP). Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and may decrease the prevalence of ROP.
  
  
  METHODS
  In a phase II pharmacokinetics and safety study, five infants (three girls) with a median (range) gestational age (GA) of 26 wk + 6 d (26 wk + 0 d to 27 wk + 2 d) and birth weight of 990 (900-1,212) g received continuous intravenous infusion of recombinant human (rh)IGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for a median (range) duration of 168 (47-168) h in dosages between 21 and 111 µg/kg/24 h.
  
  
  RESULTS
  Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (P < 0.001) than model-predicted endogenous levels. Of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within the target range, 4 (5%) were above, and 33 (45%) were below. The predicted dose of rhIGF-I/rhIGFBP-3 required to establish circulating levels of IGF-I within the intrauterine range in a 1,000 g infant was 75-100 µg/kg/24 h. No hypoglycemia or other adverse effects were recorded.
  
  
  CONCLUSIONS
  In this study, continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3, and was found to be safe.
authors.affiliation: Department of Pediatrics, Institution of Clinical Sciences, Lund University, Lund, Sweden. david.ley@med.lu.se
authors.forename: David
authors.initials: D
authors.lastname: Ley
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hansen-Pupp
authors.forename: Aimon
authors.initials: A
authors.lastname: Niklasson
authors.forename: Magnus
authors.initials: M
authors.lastname: Domellöf
authors.forename: Lena E
authors.initials: LE
authors.lastname: Friberg
authors.forename: Jan
authors.initials: J
authors.lastname: Borg
authors.forename: Chatarina
authors.initials: C
authors.lastname: Löfqvist
authors.forename: Gunnel
authors.initials: G
authors.lastname: Hellgren
authors.forename: Lois E H
authors.initials: LE
authors.lastname: Smith
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Hård
authors.forename: Ann
authors.initials: A
authors.lastname: Hellström
mesh_terms: D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D006801:Humans; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D008297:Male; D012178:Retinopathy of Prematurity / Q000517:prevention & control*; D013548:Sweden
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I