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

J. Frystyk, M. Hussain, C. Skjærbæk, N. Pørksen, E. R. Froesch, H. Ørskov

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)150-156
Number of pages7
JournalGrowth Hormone and IGF Research
Volume9
Issue number2
DOIs
StatePublished - May 1999
Externally publishedYes

Keywords

  • Free IGF-I
  • Half-life
  • IGF-I pharmacokinetics
  • rhIGF-I infusion

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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