Improvement of Intestinal Absorption of P-glycoprotein Substrate by D-tartaric Acid
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- IIDA Aiko
- Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Science
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- TOMITA Mikio
- Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Science
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- IDOTA Yoko
- Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Science
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- TAKIZAWA Yusuke
- Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Science
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- HAYASHI Masahiro
- Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Science
Bibliographic Information
- Other Title
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- Improvement of Intestinal Absorption of Pglycoprotein Substrate by Dtartaric Acid
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Abstract
The purpose of the present experiment was to examine the effects of D-tartaric acid (TA) on intestinal drug absorption under both in situ and in vitro experimental conditions. In the in vitro diffusion chamber experiments, TA (10 mM) added to the mucosal side of rat colon significantly decreased rhodamine123 (Rho 123) transport from the serosal to mucosal side. Since TA has been shown to change the integrity of the epithelial tight junctions in rat colon at low pH conditions, resulting in improved paracellular drug transport, the effect of TA on membrane resistance was examined at pH 7.4 in the present study. It was found that membrane resistance, an indicator of paracellular integrity, did not change at pH 7.4. In the in situ loop method, TA (20 mM) increased the absorption of Rho123 in both ileum and colon but not in jejunum. TA (20 mM) also increased the absorption of daunorubicin in the ileum, but TA (20 mM) did not change the expression level of P-glycoprotein (P-gp). TA (20 mM) significantly inhibited excretion of i.v.-administered Rho123 and daunorubicin into the ileal lumen. In conclusion, for the first time we demonstrated that TA increases the intestinal absorption of P-gp substrates Rho123 and daunorubicin, possibly by modulating the P-gp function without changing the expression level of P-gp in the rat intestine.<br>
Journal
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- Drug Metabolism and Pharmacokinetics
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Drug Metabolism and Pharmacokinetics 21 (5), 424-428, 2006
The Japanese Society for the Study of Xenobiotics
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Details 詳細情報について
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- CRID
- 1390282680156372736
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- NII Article ID
- 10018307141
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- NII Book ID
- AA1162652X
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- ISSN
- 18800920
- 13474367
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- Text Lang
- en
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- Data Source
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- JaLC
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed