遺伝子組換え型lnsulin-Like Growth Factor-I (rhlGF-I)の消化管吸収

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書誌事項

タイトル別名
  • Gastrointestinal Absorption of Recombinant Human Insulin-Like Growth Factor-I

抄録

The possibility of oral delivery of recombinant human insulin-like growth factor-I was investigated in rats. The degradation of 125I-rhlGF-I in the gastrointestinal (GI) contents was in the order of jejunum = ileum >> large intestine, and little degradation was found in the stomach. Some adjuvants could inhibit the degradation, especially aprotinin and casein inhibited by 70-95%. On the other hand, rhlGF-I was relatively stable in the subcellular fraction of mucosal cells (BBM, cytosol, lysosome), and there was no site difference through the intestine. The bioavailability (BA) of rhlGF-I after oral administration was 9.3%, which was much greater than that of insulin. The BA was further increased by coadministration with aprotinin and casein, indicating that the stabilization of rhlGF-I in GI tract could enhance its absorption. From the results of gel filtration chromatography of rat plasma following oral administration of 125l-rhIGF-I, the peaks in high molecular region were detected and they were thought to be macromolecular complexes which consist of 125I-rhlGF-I and IGFBP-2 and/or -3. These results strongly suggest the possibility of oral delivery of rhlGF-I.<BR> We also examined the absorption kin etics of rhlGF-I by the in situ single-pass perfusion method. The absorption clearance (CLa) of rhlGF-I was dependent on its concentration. Using acid-washing technique, rhlGF-I was found to be adsorbed acid-sensitively to the mucosal surface and the incorporation of immunoreactive rhIGF-I to the mucosal tissue was recognized at the same time. These results suggest that rhlGF-I is absorbed partly by a specialized absorption mechanism.

収録刊行物

  • 薬物動態

    薬物動態 11 (supplement), 5106-5107, 1996

    日本薬物動態学会

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