Pharmacokinetic Profile of Recombinant Human Insulin‐Like Growth Factor I Given Subcutaneously in Normal Subjects

Abstract

The pharmacokinetic profile of recombinant human insulin‐like growth factor I (IGF‐I) was studied in healthy volunteers. Following a single subcutaneous injection of 40 μg/kg or 80 µg/kg,mean serum IGF‐I concentrations increased by 150 ng/ml and 245 ng/ml, respectively. During repeated daily injections of 40 μg/kg, a steady‐state IGF‐I level of 150 ng/ml above baseline was reached. Of the pharmacokinetic indices measured, only Tmax, varied between single and multiple dose regimens (6.9 hours versus 3.5 hours). No hypoglycaemic symptoms were observed, and after injection of IGF‐I no depression of endogenous IGF‐I production was observed. Fasting insulin levels were unaltered, but insulin was lowered by IGF‐I with respect to placebo.

The effects of recombinant human insulin-like growth factor-I (IGF-I) administration on the levels of IGF-I, IGF-II and IGF-binding proteins in adolescents with insulin-dependent diabetes mellitus

“…Despite the described differences in IGF binding proteins in IDDM, which include reduced levels of IGFBP-3 and elevated IGFBP-I concentrations (Batch et al 1991, Holly et al 1990, the pharmacokinetic profile of IGF-I admin¬ istration in this study was similar to that seen in normal subjects where an identical dose and site of administration was used (Wilton et al 1991). Peak levels were achieved a little earlier than those previously described in normal individuals but the half-life of around 17 h was virtually identical.…”

Insulin-like growth factor I (IGF-I) replacement therapy increases albumin concentration in liver cirrhosis: Results of a pilot randomized controlled clinical trial

“…This might be due to the relatively low dose used and also to the fact that IGF-I was given only once daily and blood sampling was performed 24 h after the last IGF-I dose. Since in normal individuals half-life of this hormone is about 15 h [28] and might be shorter in cirrhotics due to decreased IGFBP-3 [8], the circulating levels of IGF-I in our trial could be below normal values part of the day. Future studies should define IGF-I pharmacokinetics in liver cirrhosis to allow adjusting the dose and the timing of IGF-I administration to the specific needs of these patients in order to optimize the therapeutic benefit.…”

IGF-1 and atherothrombosis: relevance to pathophysiology and therapy

“…20 h [280]. Intravenous rhIGF-1 infusions (7 and 14 μg · kg − 1 of body weight · h − 1 ) have been shown to decrease serum levels of insulin and C-peptide without affecting plasma glucose levels: the decrease in the insulin/glucose ratio was related to tissue insulin sensitivity enhanced by IGF-1 [281,282]. Metabolic and cardiovascular effects of rhIGF-1 (20 μg · kg − 1 of body weight · h − 1 ) and insulin (0.5 m-unit · kg − 1 of body weight · min − 1 ) were compared: IGF-1 infusion decreased Ra (glucose appearance rate) and increased Rd (glucose utilization rate), without changes in NEFA levels.…”