EFFECTS OF MITOMYCIN C, 5-FLUOROURACIL AND CYCLOPHOSPHAMIDE ON DRUG ABSORPTION, ENZYME ACTIVITIES AND MUCOSAL LIPID COMPOSITION OF INTESTINE
スポンサーリンク
概要
- 論文の詳細を見る
The effect of a single intravenous or oral administration of mitomycin C (MMC), 5-fluorouracil (5-FU) or cyclophosphamide (CP) on drug absorption was studied in rats in relation to changes in membrane characteristics. At 48 h after pretreatment, a differential effect on the absorption of sulfanilamide and L-tryptophan was observed in in situ recirculation experiments. Intravenous MMC administration suppressed the absorption of both sulfanilamide and L-tryptophan to a similar extent as a higher oral dose of this agent. Dosing with 5-FU via both routes caused the largest but almost equal suppression of L-tryptophan absorption. However, CP had no effect on the absorption of the two drugs. Differences in these effects were considered to reflect their pharmacological and pharmacokinetic properties. Absorption of drugs from the small intestine had a positive correlation with small intestinal wet weight regardless of the antitumor drug used, pretreatment doses and routes of administration and the results indicated that the change in absorptive surface area played a major role in this phenomenon. Toxicity to intestinal mucosa was shown to derive from an effect on dividing cells in the crypts because MMC and 5-FU preferentially decreased thymidine kinase activity. However, at the membrane level, increased mucosal membrance permeability was also confirmed by measuring the release rates of D-glucose from liposomes consisting of mucosal total lipids obtained from the antitumor drug-treated rats. Pretreatment with lipophilic and polymeric prodrugs of MMC did not exhibit any effect on drug absorption and thus, the possibility of alleviation of toxicity and adverse reactions via the prodrug approach was suggested.
- 社団法人日本薬学会の論文
著者
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Hashida Mitsuru
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Hashida Mitsuru
Faculty Of Pharmaceutical Sciences Kyoto University
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Hashida M
Departments Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University
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Sezaki H
Faculty Of Pharmaceutical Sciences Setsunan University
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SEZAKI Hitoshi
Faculty of Pharmaceutical Sciences, Kyoto University
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Sezaki H
Setsunan Univ. Osaka Jpn
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Sezaki Hitoshi
Faculty Of Pharmaceutical Sciences Kyoto University
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Sezaki Hitoshi
Faculty Of Pharmaceutical Sciences Setsunan University
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Hashida M
Department Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University
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MIZUNO MASAYUKI
Faculty of Pharmaceutical Sciences, Kyoto University
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TAMURA MASAMI
Faculty of Pharmaceutical Sciences, Kyoto University
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Mizuno Masayuki
Faculty Of Pharmaceutical Sciences Kyoto University
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Mizuno Masayuki
The Authors Are With Silicon Systems Research Laboratories Nec Corporation
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Mizuno M.
Department Of Materials Science And Engineering Kyoto University
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Sasaki Hitoshi
Faculty Of Pharmaceutical Sciences Kyoto University
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Tamura Masami
Faculty Of Pharmaceutical Sciences Kyoto University
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Sasaki H
Nagasaki Univ. School Of Medicine Nagasaki Jpn
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