Developmental changes in pharmacokinetics of recombinant human insulin- like growth factor-I in rats

Developmental changes in pharmacokinetics of recombinant human insulin- like growth factor-I (rhIGF-I) were investigated after i.v. administration to rats aged 4 and 7 weeks, as young growing rats and adult rats, respectively. rhIGF-I in the plasma declined multi-exponentially in both groups of rats. Plasma concentrations of rhIGF-I were lower at almost all the time points examined in 4 weeks old rats than 7 weeks old rats. The values of total body clearance (CL(total)) and mean residence time (MRT) indicated that rhIGF-I disappeared more rapidly in 4 weeks old rats than 7 weeks old rats at any dosage. Dose-dependent pharmacokinetics was observed in 7 weeks old rats: the higher the dosage was, the larger the value of CL(total) came to be, but not in 4 weeks old rats. The amounts of IGF-binding proteins (IGFBPs) in the plasma were assessed by determining the endogenous IGF-I, and the levels of the 150 kDa complex, a ternary complex of IGF-I with IGFPB-3 and an acid labile-subunit, were found to be lower in 4 weeks old rats than in 7 weeks old rats. In rats at 4 weeks of age, the elimination of rhIGF-I was significantly faster than for the 7 week old rats, which would be due to the lower plasma levels of IGFBP-3 in young growing rats.