1990 Fiscal Year Final Research Report Summary
Physiological and Anatomical Factors Controlling Intestinal Drug Absorption Mechanism
| Project/Area Number |
63571101
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
HAYASHI Masahiro Department of Biopharmaceutics, Tokyo College of Pharmacy, Associate Professor, 薬学部, 助教授 (20012669)
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| Co-Investigator(Kenkyū-buntansha) |
HORIE Toshiharu Department of Biopharmaceutics, Tokyo College of Pharmacy, Assistant Professor, 薬学部, 講師 (90120154)
AWAZU Shoji Department of Biopharmaceutics, Tokyo College of Pharmacy, Professor, 薬学部, 教授 (60012621)
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| Project Period (FY) |
1988 – 1990
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| Keywords | Intercellular Route / Transcellular Route / Absorptive Site Difference / Equivalent Pore Radius / Impedance Analysis / Membrane Perturbation / Blood Flow Dependence / Simultaneous Luminal and Vascular Perfusion |
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| Research Abstract |
As two factors controlling drug absorption mechanism, permeation routes and blood flow dependence were analyzed. The colonic and jejunal absorption of poorly-absorbed cefmetazole were enhanced by sodium caprate (C10) in the rat. Its enhancing effects was greater in the colon than in the jejunum.
For the intercellular (paracellular) pathways in the colon, C10 increased the equivalent pore radii ; C10 increased permeability through large and small pores which was obtained from the relationship between the membrane permeability of water-soluble non-electrolytes with various molecular weights and their free diffusion coefficients. Impedance analysis showed that C10 decreased the junctional resistance and increased the membrane capacitance, supporting the increase in junctional leakiness and the enlargement of intercellular space. For the intercellular pathways in the jejunum, no C10 effect was found. The similar site-dependent enhancement was observed also by the voltage clamp method.
For th
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e transcellular pathway, fluorescence polarization technique showed that membrane perturbation through the interaction between C10 and membrane protein or lipids enhances the membrane permeability. Transcellular permeability increased by C10 was greater in the jejunum than in the colon. Consequently, the difference between the effects of C10 on the jejunal and colonic absorption of cefmetazole was considered to be due mainly to the difference in its effects on the intercellular pathway.
For the blood flow dependent drug absorption, simultaneous luminal and vascular perfusion using the perfluorochemical emulsion as a vascular perfusate was examined. This emulsion was found to retain its normal barrier functions for drug transport. The contribution of blood flow resistance to total resistance of antipyrine absorption exceeded that for salicylic acid absorption. The effects of albumin the vascular perfusate on drug absorption is now under investigation from the direct action of albumin on the capillary wall. Less
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Research Products
(12 results)
