DEVELOPMENTAL-CHANGES IN PHARMACOKINETICS OF RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR-I RATS

Developmental changes in pharmacokinetics of recombinant human insulin -like growth factor-I (rhIGF-I) were investigated after i.v. administr ation 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 al most all the time points examined in 4 weeks old rats than 7 weeks old rats, The values of total body clearance (CLtotal) 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 pharmaco kinetics was observed in 7 weeks old rats: the higher the dosage was, the larger the value of CLtotal came to be, but not in 4 weeks old rat s. The amounts of IGF-binding proteins (IGFBPs) in the plasma were ass essed by determining the endogenous IGF-I, and the levels of the 150 k Da 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 o ld rats. In rats at 4 weeks of age, the elimination of rhIGF-I was sig nificantly faster than for the 7 week old rats, which would be due to the lower plasma levels of IGFBP-3 in young growing rats.