Investigation of intestinaL absorption and the mechanisms of ionized drugs using simultaneous luminal and vascular perfusion of rat small intestine
| Project/Area Number |
61490001
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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 |
広領域
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| Research Institution | Hokkaido University |
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Principal Investigator |
MIYAZAKI Katsumi (1987) Hokkaido University Hospital, 医学部附属病院, 教授 (30166144)
宮崎 勝己 (1987) 北海道大学, 医学部, 助教授
有田 隆一 (1986) 北海道大学, 医学部, 教授 (40001028)
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| Co-Investigator(Kenkyū-buntansha) |
宮崎 勝巳 北海道大学, 医学部附属病院, 助教授 (30166144)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1987: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1986: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Keywords | simultaneous luminal and vascular perfusion / intestinal absorption / transport mechanism / quaternary ammonium compound / <beta>-lactam antibiotics / 吸収抑制 / β-ラクタム抗生物質 / アミノ酸 / ジペプチド |
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| Research Abstract |
A method is described which allows simultaneous vascular and luminal perfusion of the jejunal segment of rat intestine.Perfluorochemical arteificial blood (FC-43 Emulsion)was utilized as a vascular perfusion medium.The viability of this preparation can be maintained as indicated by morphological findings, competitive inhibition between L-phenylalanine and L-methionine,and the transport of L-phenylalanine against a concentration gradient.This preparation was used for investigation of the transport behavior of several amino -lactam antibiotics by using a more sensitive and a reproducible high-performance liquid chromatographic assay which we have developed for amino -lactam antibiotics. Aminocephalosporins(cephradine and cephalexin)disappeared rapidly in venous effluent compared to ampicillin.This technique directly demonstrated that there were significant differences in the venous appearance rate between aminocephalosporins and ampicillin.
Xompetitive inhibitory benavior among amino -lactam antibiotics in the rat intestinal absorption process was examined.The venous appearances of cephradine and cephalexin were significantly inhibited by cyclacillin,and other aminopenicillins.In a contrast,the venous appearance of these amino- cephalosporins was not significantly reduced by amino acids and dipeptides. These results suggested that a common absorption mechanism which differed from the carrier-mediated transport systems of amino acids and dipeptides participated in the intestinal absorption process of these drugs.
On the other hand,the transport characteristics of propantheline,a quaternary ammonium compound,has been studied using this simultanious perfusion technique, the binding of propantheline to intestinal tissue was observed in the earlier step of absorption process.
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Report
(2 results)
Research Products
(10 results)
