Simulation of IGF-I pharmacokinetics after infusion of recombinant IGF-I in human subjects.
The pharmacokinetics of recombinant human insulin-like growth factor I (IGF-I) were studied in four healthy volunteers by a 3-h infusion at a rate of 20 micrograms.kg-1.h-1. A compartmental model was used to simulate the plasma "free" IGF-I and IGF-I associated with the 50- and 150-kDa plasma protein fractions. The model is based on the concept that free IGF-I and IGF binding proteins (IGFBPs) are the substrates for their own degradation and that they act as reservoirs for retention of IGF-I in the vascular compartment or inhibiting IGF-I action. The metabolic clearance rate (MCR) of free IGF-I is estimated as 2.62 +/- 0.94 ml.min-1.min-1 with a production rate of 4.75 +/- 1.74 mg/day (621.0 +/- 227.34 nmol/day). The simulation shows that higher concentrations of IGFBP-3 would increase the estimate of MCR for free IGF-I by reducing free IGF-I concentration. The model will be of value for simulation of dynamic profiles of free IGF-I and receptor-bound IGF-I in a variety of pathophysiological conditions.
Boroujerdi
M A
MA
Division of Medicine, United Medical School, London, United Kingdom.
Jones
R H
RH
Sönksen
P H
PH
Russell-Jones
D L
DL
D003198:Computer Simulation; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D011994:Recombinant Proteins; D012680:Sensitivity and Specificity
D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I