title: A pharmacokinetic and dosing study of intravenous insulin-like growth factor-I and IGF-binding protein-3 complex to preterm infants.
abstract: In preterm infants, low levels of insulin like growth factor 1 (IGF-I) have been associated with impaired growth and retinopathy of prematurity. Our objective was to study safety and pharmacokinetics of i.v. administered rhIGF-I with its binding protein 3 (rhIGFBP-3) to preterm infants. At 3 d chronological age, an i.v. 3 h infusion of rhIGF-I/rhIGFBP-3 was administered followed by serial measurements of IGF-I and IGFBP-3. Infants were evaluated for physiologic safety measurements. The individual dose of rhIGF-I ranged from 1 to 12 microg/kg. The study was conducted at Queen Silvia Children's Hospital, Gothenburg, Sweden, between January and November 2007. Five patients (3 F) with mean (range) post menstrual age 27 wk (26-29) and birth weight 1022 g (810-1310) participated. IGF-I and IGFBP-3 levels before infusion were median (range) 18 (12-28) and 771 (651-1047) ng/mL, respectively. Immediately after study drug infusion, serum IGF-I and IGFBP-3 levels were 38 (25-59) and 838 (754-1182) ng/mL, respectively. Median (range) half-life for IGF-I and IGFBP-3 was 0.79 (0.59-1.42) and 0.87 (0.85-0.94) hours, respectively. Blood glucose, insulin, sodium, potassium, and physiologic safety measures were within normal ranges. The rhIGF-I/rhIGFBP-3 equimolar proportion was effective in increasing serum IGF-I levels and administration under these study conditions was safe and well tolerated.
authors.affiliation: Department of Ophthalmology, Sahlgrenska Academy at Gothenburg University, Göteborg 416 85, Sweden.
authors.forename: Chatarina
authors.initials: C
authors.lastname: Löfqvist
authors.forename: Aimon
authors.initials: A
authors.lastname: Niklasson
authors.forename: Eva
authors.initials: E
authors.lastname: Engström
authors.forename: Lena E
authors.initials: LE
authors.lastname: Friberg
authors.forename: Cecilia
authors.initials: C
authors.lastname: Camacho-Hübner
authors.forename: David
authors.initials: D
authors.lastname: Ley
authors.forename: Jan
authors.initials: J
authors.lastname: Borg
authors.forename: Lois E H
authors.initials: LE
authors.lastname: Smith
authors.forename: Ann
authors.initials: A
authors.lastname: Hellström
mesh_terms: D001724:Birth Weight; D005260:Female; D005865:Gestational Age; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007262:Infusions, Intravenous; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I