Role of Transporter and Metabolic Enzyme in Intestinal Drug Absorption.
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Accession number;00A0997675
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| Title;Role of Transporter and Metabolic Enzyme in Intestinal Drug Absorption. |
| Author;
MIZUMA TAKASHI
(Tokyo Coll. of Pharm., Fac. of Pharm. Sci.)
MATSUMOTO SEIICHI
(Tokyo Coll. of Pharm., Fac. of Pharm. Sci.)
HAGI KATSURA
(Tokyo Coll. of Pharm., Fac. of Pharm. Sci.)
KOYANAGI AKIHIRO
(Tokyo Coll. of Pharm., Fac. of Pharm. Sci.)
NARASAKA TAKUO
(Tokyo Coll. of Pharm., Fac. of Pharm. Sci.)
FUSEDA NORIHIKO
(Tokyo Coll. of Pharm., Fac. of Pharm. Sci.)
HAYASHI MASAHIRO
(Tokyo Coll. of Pharm., Fac. of Pharm. Sci.)
AWAZU SHOJI
(Tokyo Coll. of Pharm., Fac. of Pharm. Sci.)
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Journal Title;Xenobiotic Metabolism and Disposition
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Journal Code:X0758A
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ISSN:0916-1139
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VOL.15;NO.Supplement;PAGE.S100-S101(2000)
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| Figure&Table&Reference;FIG.1, TBL.1, REF.5 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;We have studied intestinal metabolism and transport, which is considered as sequential(1) or competitive(2) process in absorption. (1) Disaccharide(maltose, cellobiose, lactose) conjugates of p-nitrophenol were hydrolyzed to p-nitrophenyl .BETA.-glucosides(p-NP.BETA.glc) on the mucosal side. p-NP.BETA.glc was transported by Na*/glucose cotransporter(SGLT1). Transport clearance of p-NP.BETA.glc formed from cellobiose and lactose conjugates of p-NP were higher than that from maltose or of p-NP.BETA.glc itself. These results suggest that SGLT1 may be cooperatively coupled with lactase/phloridzin hydrolase catalizing hydrolysis of cellobiose and lactose conjugates. There might be cooperative relationship between peptidase and H+/oligopeptide cotransporter or amino acid transporter as well. (2) Kyotorphin(KTP) was to unstable in intestine to be absorbed. KTP appeared on the serosal side in the presence of peptidase inhibitors. Meanwhile, cyclic KTP was stable in intestine to be absorbed. Absorption clearance of cyclic KTP was higher than the overall transport clearance of KTP, which was calculated according to the metabolic inhibition model. These results indicate that metabolism degradation and membrane transport are competitive. Unless drug is stabilized against metabolic enzyme, intestinal absorption of drug can not be improved even if membrane transport is increased. (author abst.) |
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