Simulation of igf-i pharmacokinetics following infusion of
recombinant igf-i in human subjects.
Boroujerdi, Massoud A., Richard H. Jones, Peter. H. Sonksen, David. L.
Russell-Jones.
Division of Medicine, United Medical and Dental Schools, St Thomas'
Campus, London SE1 7EH, United Kingdom
APStracts 4:0074E, 1997.
The pharmacokinetics of recombinant insulin-like growth factor one (rh
IGF-I) were studied in four healthy volunteers by a three hour
infusion at a rate of 20 ug/kg/h. A compartmental model was used to
simulate the plasma $QUOTfree$QUOT IGF-I and IGF-I associated with
the 50 kD and 150 kD 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 reserviors
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/kg 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 $QUOTfree$QUOT IGF
-I and receptor bound IGF-I in a variety of pathophysiological
conditions.
Received 9 August 1996; accepted in final form 26 March 1997.
APS Manuscript Number E388-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 3 April 1997