PT  - JOURNAL ARTICLE
AU  - Kazutaka Higaki
AU  - Yukihiro Matsumoto
AU  - Rika Fujimoto
AU  - Yuji Kurosaki
AU  - Toshikiro Kimura
TI  - Pharmacokinetics of Recombinant Human Insulin-Like Growth Factor-I in Diabetic Rats  
DP  - 1997 Nov 01
TA  - Drug Metabolism and Disposition
PG  - 1324--1327
VI  - 25
IP  - 11
4099  - http://dmd.aspetjournals.org/content/25/11/1324.short
4100  - http://dmd.aspetjournals.org/content/25/11/1324.full
SO  - Drug Metab Dispos1997 Nov 01; 25
AB  - Pharmacokinetics of recombinant human insulin-like growth factor-I (rhIGF-I) was investigated after iv administration (0.32, 1.0, and 3.2 mg/kg) to normal and streptozotocin-induced diabetic rats. rhIGF-I was eliminated from plasma biexponentially in both normal and diabetic rats. Plasma concentrations of rhIGF-I were lower at almost all the time points examined in diabetic rats than in normal rats. The pharmacokinetic parameters of total body clearance (CLtotal), mean residence time (MRT), and elimination rate constant (kel) indicated that rhIGF-I disappeared more rapidly in diabetic rats than in normal rats at any dosage. The amounts of IGF binding proteins (IGFBPs) in plasma were assessed by determining the endogenous IGF-I and. Levels of the 150 kDa complex, a ternary complex of IGF-I with IGFPB-3 and an acid-labile subunit, the 50 kDa complex, a complex of IGF-I with IGFBP-2, were found to be lower in diabetic rats than in normal rats. Fractions of rhIGF-I free and bound to the binding proteins were estimated by gel chromatographic separation of rhIGF-I in plasma after iv administration, and the pharmacokinetics of free and bound rhIGF-I was analyzed independently. Plasma concentrations of free and bound rhIGF-I were lower in diabetic rats than in normal rats, especially the concentrations of the 150 kDa complex were much lower. The reduced IGFBP-3 would be responsible for the faster elimination of rhIGF-I in diabetic rats. The American Society for Pharmacology and Experimental Therapeutics