The pharmacokinetics of free insulin-like growth factor-I in healthy subjects

In a randomized cross-over study in five healthy males we compared 75-min c onstant i.v. infusion of saline, low-dose recombinant human (rh) insulin-li ke growth factor-I (rhIGF-I; 1,5 mu g/kg/h) and high-dose rhIGF-I (9.0 mu g /kg/h). Serum samples were analysed for ultrafiltered free IGF-I (fIGF-I), total IGF-I (tIGF-I), tIGF-II and IGF-binding protein-1 (IGFBP-1) and -3. Free and total IGF-I were unchanged during saline infusion. Low-dose rhIGF- I caused a small increment in fIGF-I [+41%, from 0.64 +/- 0.19 (mean +/- SE M) to 0.90 +/- 0.25 mu g/l; P < 0.05] and tIGF-I (+9%, from 220 +/- 31 to 2 39 +/- 33 mu g/l; P < 0.05). High-dose rhIGF-I increased tIGF-I by 40% (fro m 227 +/- 36 to 329 +/- 31 mu g/l; P < 0.05), and fIGF-I by 11.5 times (fro m 0.56 +/- 0.20 to 6.46 +/- 1.39 mu g/l; P < 0.05). The pharmacokinetic pro file of fIGF-I was calculated after high-dose IGF-I only. The disappearance of fIGF-I followed first order kinetics with an apparent half-life of 14.4 +/- 1.0 [11.2-17.1 (range)] min. The clearance was estimated to 52 +/- 20 (16-128) ml/min/kg and the volume of distribution to 1102 +/- 464 (388-2899 ) ml/kg. In the three experiments, there were no differences in IGFBP-1, an d tlGF-II and IGFBP-3 remained unchanged. In conclusion, fIGF-I remained within the physiological range after low-dos e rhIGF-I, whereas high-dose rhIGF-I resulted in supraphysiological concent rations. Since the half-life estimates for each subject were remarkably sim ilar, this parameter most likely does not explain the observed variation in clearance and volume of distribution of fIGF-I. Instead, differences in th e circulating and cellular IGF-I binding capacity may be of importance, (C) 1999 Churchill Livingstone.