Abstract
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 (CL(total)), mean residence time (MRT), and elimination rate constant (k(el)) indicated that rhIGF-I disappeared more rapidly in diabetic rats than in normal rata 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1324-1327 |
| Number of pages | 4 |
| Journal | Drug Metabolism and Disposition |
| Volume | 25 |
| Issue number | 11 |
| Publication status | Published - Nov 1997 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Pharmacology
- Toxicology
Cite this
Pharmacokinetics of recombinant human insulin-like growth factor-I in diabetic rats. / Kimura, Toshikiro; Higaki, Kazutaka; Matsumoto, Yukihiro; Fujimoto, Rika; Kurosaki, Yuji.
In: Drug Metabolism and Disposition, Vol. 25, No. 11, 11.1997, p. 1324-1327.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacokinetics of recombinant human insulin-like growth factor-I in diabetic rats
AU - Kimura, Toshikiro
AU - Higaki, Kazutaka
AU - Matsumoto, Yukihiro
AU - Fujimoto, Rika
AU - Kurosaki, Yuji
PY - 1997/11
Y1 - 1997/11
N2 - 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 (CL(total)), mean residence time (MRT), and elimination rate constant (k(el)) indicated that rhIGF-I disappeared more rapidly in diabetic rats than in normal rata 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.
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 (CL(total)), mean residence time (MRT), and elimination rate constant (k(el)) indicated that rhIGF-I disappeared more rapidly in diabetic rats than in normal rata 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.
UR - http://www.scopus.com/inward/record.url?scp=0343554634&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0343554634&partnerID=8YFLogxK
M3 - Article
VL - 25
SP - 1324
EP - 1327
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
SN - 0090-9556
IS - 11
ER -