Pharmacokinetics of recombinant human insulin-like growth factor-I in diabetic rats

Toshikiro Kimura, Kazutaka Higaki, Yukihiro Matsumoto, Rika Fujimoto, Yuji Kurosaki

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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 languageEnglish
Pages (from-to)1324-1327
Number of pages4
JournalDrug Metabolism and Disposition
Volume25
Issue number11
Publication statusPublished - Nov 1997
Externally publishedYes

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Pharmacokinetics
Insulin-Like Growth Factor I
Rats
Plasmas
Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor Binding Protein 3
Streptozocin
Rate constants
Carrier Proteins
Gels

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 journalArticle

Kimura, Toshikiro ; Higaki, Kazutaka ; Matsumoto, Yukihiro ; Fujimoto, Rika ; Kurosaki, Yuji. / Pharmacokinetics of recombinant human insulin-like growth factor-I in diabetic rats. In: Drug Metabolism and Disposition. 1997 ; Vol. 25, No. 11. pp. 1324-1327.
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