GASTROINTESTINAL ABSORPTION OF RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR-I IN RATS

The GI absorption of recombinant human insulin-like growth factor-I (r hIGF-I) and its improvement were investigated in rats. The I-125-rhIGF -I rapidly degraded to the trichloroacetic acid-soluble form in the sm all-intestinal contents, but it was relatively stable in the gastric a nd large-intestinal contents and in the subcellular fraction of the sm all-intestinal mucosa. To protect rhIGF-I from degradation in the smal l-intestinal contents, the effect of some adjuvants was examined and t heir degradation was markedly inhibited by the presence of aprotinin o r casein. After p.o. administration of I-125-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 r hIGF-I was absorbed into the systemic circulation and that the bioavai lability was 9.3%, which is much greater than that of insulin. The coa dministration of aprotinin and that of casein enhanced the bioavailabi lity 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 radioac tivity in the plasma was found to be in the form of high-molecular-wei ght complexes. The mechanism for the uptake of rhIGF-I by intestinal m ucosa may be absorptive-mediated endocytosis.