Pharmacodynamic considerations with recombinant human insulin-like growth factor-I in children.
OBJECTIVE
To report effects of weight-based recombinant human insulin-like growth factor-I (rhIGF-I) on IGF axis parameters in children with hyperinsulinism.


METHODS
Open label trial with subcutaneous rhIGF-I (40 microg/kg/dose). Patients studied were children (1 month to 11 years) with diffuse hyperinsulinism (n = 7). Serial serum IGF and insulin-like growth factor binding protein (IGFBP) concentrations were measured by RIA and analyzed by linear Pearson regression.


RESULTS
Following the initial rhIGF-I dose, total insulin-like growth factor-I (IGF-I) rose by 56% at 30 min (p < 0.01) and 85% at 120 min (p < 0.02). Serum IGF-II, IGFBP-2, and IGFBP-3 levels did not change. Peak serum IGF-I levels within 12 h of the initial rhIGF-I dose were 167-700 mg/ml. The variable peak IGF-I response is attributable in part to IGFBP-3 differences across this pediatric age range. Models of rhIGF-I dosing based upon body surface area (BSA) or initial IGFBP-3 resulted in predictable peak serum IGF-I levels (r = 0.78; p < 0.03). Recalculating rhIGF-I dosing based upon the BSA . IGFBP-3 product correlated closely with peak IGF-I level (r = 0.85; p < 0.007).


CONCLUSIONS
Weight-based IGF-I dosing in this cohort resulted in variable IGF-I levels. Considering BSA and serum IGFBP-3 concentration in children is appropriate for subcutaneous IGF-I administration. A combination of these values may yield predictable individualization of rhIGF-I dosing.
Ferry
Robert J
RJ
Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, The University of Texas Health Science Center at San Antonio, Tex., USA.
Cohen
Pinchas
P
Levitt Katz
Lorraine E
LE
D001830:Body Surface Area; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000188:drug therapy*; D007223:Infant; D007279:Injections, Subcutaneous; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics
D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II