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 mu g.kg(-1).h(-1). A compartmental model was used to simul ate the plasma ''free'' IGF-I and IGF-I associated with the 50- and 15 0-kDa plasma protein fractions. The model is based on the concept that free IGF-I and IGF binding proteins (IGFBPs) are the substrates for t heir own degradation and that they act as reservoirs for retention of IGF-I in the vascular compartment or inhibiting IGF-I action. The meta bolic 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 (62 1.0 +/- 227.34 nmol/day). The simulation shows that higher concentrati ons of IGFBP-3 would increase the estimate of MCR for free IGF-I by re ducing free IGF-I concentration. The model will be of value for simula tion of dynamic profiles of free IGF-I and receptor-bound IGF-I in a v ariety of pathophysiological conditions.