Gastrointestinal absorption of recombinant human insulin-like growth factor-I in rats.
نویسندگان
چکیده
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.
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ورودعنوان ژورنال:
- The Journal of pharmacology and experimental therapeutics
دوره 283 2 شماره
صفحات -
تاریخ انتشار 1997