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

Ley, DavidHansen-Pupp, IngridNiklasson, AimonDomellöf, MagnusFriberg, Lena E.Borg, JanLöfqvist, ChatarinaHellgren, GunnelSmith, LoisHård, Anna-LenaHellström, Ann2017-08-172012Ley, David, Ingrid Hansen-Pupp, Aimon Niklasson, Magnus Domellöf, Lena E. Friberg, Jan Borg, Chatarina Löfqvist, et al. 2012. 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. Pediatric Research 73, no. 1: 68–74. doi:10.1038/pr.2012.146.0031-3998http://nrs.harvard.edu/urn-3:HUL.InstRepos:33776196BACKGROUND: 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. CONCLUSION: 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.en-USLongitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants: pharmacokinetics and short-term safetyJournal Article2017-08-1710.1038/pr.2012.146