TY - JOUR
T1 - The pharmacokinetics of free insulin-like growth factor-I in healthy subjects
AU - Frystyk, J.
AU - Hussain, M.
AU - Skjærbæk, C.
AU - Pørksen, N.
AU - Froesch, E. R.
AU - Ørskov, H.
N1 - Funding Information:
This study was supported by grants from the Danish Health Research Council (grant no. 9601222), the Danish Health Research Council [Aarhus University – Novo Nordisk Centre for Research in Growth and Regeneration (grant no. 9600822)], the Institute of Experimental Clinical Research, University of Aarhus, the Swiss National Science Foundation and the Desiree and Niels Yde Foundation. We are indebted to Mrs A. Mengel, Mrs Y. Glanz, Mrs A. Keller, Mrs K. Nyborg Rasmussen, Mrs S. Sørensen, Mrs J. Hansen and Mrs I. Bisgaard for skilled technical assistance.
PY - 1999/5
Y1 - 1999/5
N2 - In a randomized cross-over study in five healthy males we compared 75- min constant i.v. infusion of saline, low-dose recombinant human (rh) insulin-like growth factor-I (rhIGF-I; 1.5 μg/kg/h) and high-dose rhIGF-I (9.0 μg/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 ± SEM) to 0.90 ± 0.25 μg/l; P < 0.05] and tIGF-I (+9%, from 220 ± 31 to 239 ± 33 μg/l; P < 0.05). High-dose rhIGF-I increased tIGF-I by 40% (from 227 ± 36 to 329 ± 31 μg/l; P < 0.05), and fIGF-I by 11.5 times (from 0.56 ± 0.20 to 6.46 ± 1.39 μg/l; P < 0.05). The pharmacokinetic profile 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, and tIGF-II and IGFBP-3 remained unchanged. In conclusion, fIGF-I remained within the physiological range after low-dose rhIGF-I, whereas high-dose rhIGF-I resulted in supraphysiological concentrations. Since the half-life estimates for each subject were remarkably similar, this parameter most likely does not explain the observed variation in clearance and volume of distribution of fIGF-I. Instead, differences in the circulating and cellular IGF-I binding capacity may be of importance.
AB - In a randomized cross-over study in five healthy males we compared 75- min constant i.v. infusion of saline, low-dose recombinant human (rh) insulin-like growth factor-I (rhIGF-I; 1.5 μg/kg/h) and high-dose rhIGF-I (9.0 μg/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 ± SEM) to 0.90 ± 0.25 μg/l; P < 0.05] and tIGF-I (+9%, from 220 ± 31 to 239 ± 33 μg/l; P < 0.05). High-dose rhIGF-I increased tIGF-I by 40% (from 227 ± 36 to 329 ± 31 μg/l; P < 0.05), and fIGF-I by 11.5 times (from 0.56 ± 0.20 to 6.46 ± 1.39 μg/l; P < 0.05). The pharmacokinetic profile 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, and tIGF-II and IGFBP-3 remained unchanged. In conclusion, fIGF-I remained within the physiological range after low-dose rhIGF-I, whereas high-dose rhIGF-I resulted in supraphysiological concentrations. Since the half-life estimates for each subject were remarkably similar, this parameter most likely does not explain the observed variation in clearance and volume of distribution of fIGF-I. Instead, differences in the circulating and cellular IGF-I binding capacity may be of importance.
KW - Free IGF-I
KW - Half-life
KW - IGF-I pharmacokinetics
KW - rhIGF-I infusion
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U2 - 10.1054/ghir.1999.0100
DO - 10.1054/ghir.1999.0100
M3 - Article
C2 - 10373348
AN - SCOPUS:0033136851
SN - 1096-6374
VL - 9
SP - 150
EP - 156
JO - Growth Hormone and IGF Research
JF - Growth Hormone and IGF Research
IS - 2
ER -