Pharmacokinetics and Pharmacodynamics of Recombinant Human Insulin-Like Growth Factor

Recombinant human insulin-like growth factor (rhIGF-I) was evaluated in 18 healthy males to determine its effects on serum glucose, its relationship of total IGF levels to serum glucose response and dose proportionality when administered intravenously (IV) and subcutaneously (SQ). One group of six subjects received 60, 120, and 180 &mgr;g kg(minus sign1) IV over 8 h, 1 week apart, and three groups of four subjects received 60, 120, and 180 &mgr;g kg(minus sign1) IV over 8 h, and then 1 week later received 60, 120, and 90 &mgr;g kg(minus sign1) SQ of rhIGF-I, respectively. During each dosing period, placebo and then rhIGF-I was administered on two consecutive days. Intravenous and subcutaneous does of rhIGF-I demonstrated significant decreases in glucose levels as compared to placebo that did not correspond to peak total IGF levels. Sequential repeat administration of IV infusions of rhIGF-I in a single group of subjects demonstrated significant dose-dependent increases, whereas single administration of the doses in three groups of subjects failed to demonstrate dose dependency for either the IV or subcutaneous routes of administration. These findings suggest that saturation of the binding proteins and sites occurred at the lowest dose (60 &mgr;g kg(minus sign1)) evaluated.