PREDICTION AND OPTIMIZATION OF DRUG ABSORPTION FROM THE GASTRO-INTESTINAL TRACT
| Project/Area Number |
05454565
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | SETSUNAN UNIVERSITY |
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Principal Investigator |
SEZAKI Hitoshi SETSUNAN UNIVERSITY,PHARMACY,PROFESSOR, 薬学部, 教授 (50025681)
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| Co-Investigator(Kenkyū-buntansha) |
TAKI Yoko SETSUNAN UNIVERSITY,PHARMACY,RESEARCH ASSISTANT, 薬学部, 研究員 (90258088)
SAKANE Toshiyasu SETSUNAN UNIVERSITY,PHARMACY,RESEARCH ASSOCIATE, 薬学部, 助手 (50215638)
YAMASHITA Shinji SETSUNAN UNIVERSITY,PHARMACY,ASSOCIATE PROFESSOR, 薬学部, 助教授 (00158156)
NADAI Tanekazu SETSUNAN UNIVERSITY,PHARMACY,PROFESSOR, 薬学部, 教授 (80076710)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1993: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | oral administration / drug absorption / intestinal perfusion / cultured human cell line / pharmacokinetic model / peptide drug / 吸収速度定数 / 酵素阻害剤 / 膜透過性 / Caco-2単層膜 / 薬物吸収モデル |
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| Research Abstract |
This research was undertaken to predict and improve the drug absorption from human GI tract after oral administration. New pharmacokinetic absorption model was proposed in which the human absorption processes were reconstituted mathematically from the animal data obtained in in vitro or in situ experiments.
1. Calculation of intrinsic drug permeability and its correlation with human absorption
Intrinsic parameters for drug permeation were calculated from rat intestinal perfusion experiment or in vitro permeation experiment using the monolayr of cultured human cell line. In the case of passively absorbed drugs, good correlation was observed between the obtained parameters and human drug absorption. In addition, it was proved that the mean time required for drug absorption is an important parameter to consider the real absorption process in human, as well as the permeability to intestinal membrane.
2. Constitution of new pharmacokinetic model for drug absorption
Since the simple first-order absorption model failed to describe the whole absorption process of drugs, the new model was constituted which takes into consider the drug movement along the GI tract, the volume change in the GI tract due to water absorption. It was proved that the new model is useful to describe the blood concentration profiles of drugs after oral administration.
3.Constitution of absorption model for peptide drugs
The absorption processes of enkephalin derivatives in rat small intestine were investigated. By calculating the clearances for the degradation and the permeation from the intestinal tract, the bioavailability of enkephalin derivatives after oral administration was predicted using above pharmacokinetic model. This method was useful to demonstrate the possibility of oral delivery system for such peptide drugs.
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Report
(3 results)
Research Products
(6 results)
