Effect of recombinant human growth hormone and insulin-like growth factor-1 administration on IGF-1 and IGF-binding protein-3 levels in brain injury.
OBJECTIVE
To assess the effect of recombinant human growth hormone (rhGH) on the insulin-like growth factor-1 (IGF-1) plasma concentration versus time profile during continuous infusion of recombinant human (rh)IGF-1 to patients with traumatic brain injury (TBI).


METHODS
University of Kentucky Chandler Medical Center.


METHODS
Twenty-three patients with TBI (aged 18-59 yrs) with Glascow Coma Scale scores of 4-10.


METHODS
Patients were randomized to receive rhIGF-1 0.01 mg/kg/hour and daily subcutaneous doses of rhGH 0.05 mg/kg/day or saline for 14 days.


RESULTS
Plasma concentrations of IGF-1 and IGF-binding protein (BP)-3 were quantified by radioimmunoassay. Patients receiving rhIGF-1/rhGH reached a peak IGF-1 concentration (1199.3+/-84.0 microg/L) at 72 hours and maintained it throughout the study. Levels of IGF-1 in the control group did not change significantly above baseline throughout the study. Concentrations of IGFBP-3 were significantly higher after 48 hours in the treated group (5.1+/-0.4 mg/L) than in controls (2.9+/-0.5 mg/L) and continued until the end of the study (p<0.05).


CONCLUSIONS
Infusion of rhIGF-1 in conjunction with rhGH effectively achieved and maintained supraphysiologic IGF-1 plasma concentrations throughout the dosing period in patients with TBI. It appears that rhGH alters the IGF-1 plasma concentration versus time profile during continuous administration. Although speculative, changes in protein binding of IGF-1 are the most likely mechanism.
Rockich
K T
KT
Division of Pharmaceutical Sciences, University of Kentucky College of Pharmacy and University of Kentucky Chandler Medical Center, Lexington 40536-0082, USA.
Hatton
J C
JC
Kryscio
R J
RJ
Young
B A
BA
Blouin
R A
RA
D000293:Adolescent; D000328:Adult; D001930:Brain Injuries / Q000097:blood*; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D008875:Middle Aged; D011863:Radioimmunoassay; D011994:Recombinant Proteins; D013997:Time Factors
D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I