Gastrointestinal absorption of recombinant human insulin-like growth factor-I in rats

Toshikiro Kimura, Yusuke Murakawa, Misako Ohno, Seiji Ohtani, Kazutaka Higaki

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32 Citations (Scopus)

Abstract

The GI absorption of recombinant human insulin-like growth factor-I (rhIGF-I) and its improvement were investigated in rats. The 125I-rhIGF-I rapidly degraded to the trichloroacetic acid-soluble form in the small- intestinal contents, but it was relatively stable in the gastric and large- intestinal contents and in the subcellular fraction of the small-intestinal mucosa. To protect rhIGF-I from degradation in the small-intestinal contents, the effect of some adjuvants was examined and their degradation was markedly inhibited by the presence of aprotinin or casein. After p.o. administration of 125I-rhIGF-I at the dose of 1.0 mg/kg, trichloroacetic acid- precipitable radioactivity in the plasma was periodically determined. We found that a considerable amount of rhIGF-I was absorbed into the systemic circulation and that the bioavailability was 9.3%, which is much greater than that of insulin. The coadministration of aprotinin and that of casein enhanced the bioavailability further: 46.9% and 67.0%, respectively. Radioimmunoassay using a monoclonal antibody for rhIGF-I confirmed the high bioavailability of immunoreactive rhIGF-I. From gel chromatography of plasma, the radioactivity in the plasma was found to be in the form of high- molecular-weight complexes. The mechanism for the uptake of rhIGF-I by intestinal mucosa may be absorptive-mediated endocytosis.

Original languageEnglish
Pages (from-to)611-618
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume283
Issue number2
Publication statusPublished - Nov 1 1997

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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