Intestinal Cytochrome P450 and Response to Rifampicin in Rabbits

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概要

• 論文の詳細を見る

• Properties of cytochrome P450(P450)in rabbit intestines have been investigated to assess the possibility of an experimental model for human intestinal oxidation of drugs.Significant amounts of P450 and cytochrome b5 and activities of NADPH-cytochrome P450 reductase were detected in microsomes from rabbit duodenal, jejunal, ileac and colon mucosa.All the small intestinal fractions mediated phenytoin, dextromethorphan and testosterone oxidations.Several P450 forms belonging to the CYP1A, CYP2C, CYP2D and CYP3A, but not CYP2B and CYP2E, subfamilies were detected in these tissues by Western blotting.A good correlation was observed between immunodetectable levels of CYP3A and activities of testosterone 6β-hydroxylation.Small intestine, but not colon, CYP3A levels were increased by the pretreatment of rabbits with rifampicin(50mg/kg for 4 days, p.o.).The extent of the increase was similar between duodena and livers.These properties of rabbit intestinal P450s were comparable to those of human intestine.These phenomena suggest the possibility that the rabbit is a beneficial in vivo model for the assessment of drug interaction occurring at the first pass of drugs ingested.

• 社団法人 日本薬理学会の論文
• 2000-03-01

著者

• Nakamura Takahiro

  Drug Safety Research Laboratories, Shin Nippon Biomedical Laboratories, Ltd.

• Yamazoe Yasushi

  Drug Metabolism And Molecular Toxicology Graduate School Of Pharmaceutical Sciences Tohoku Universit

• OKADA Keizo

  Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku Univers

• NAGATA Kiyoshi

  Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku Univers

• Okada Keizo

  Drug Metabolism And Molecular Toxicology Graduate School Of Pharmaceutical Sciences Tohoku Universit

• Nagata Kiyoshi

  Drug Metabolism And Molecular Toxicology Graduate School Of Pharmaceutical Sciences Tohoku Universit

• Nakamura T

  Drug Metabolism And Molecular Toxicology Graduate School Of Pharmaceutical Sciences Tohoku Universit

• Nakamura Takahiro

  Drug Safety Research Laboratories Shin Nippon Biomedical Laboratories Ltd.

関連論文

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• Evaluation methods for lymphocyte subsets in the peripheral blood of cynomolgus monkeys (IMMUNE AND ALLERGIC SYSTEM) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
• Immunotoxicity studies in non-human primates(WORKSHOP 4 : NEW TECHNOLOGY AND EVALUATIONS OF IN VIVO TOXICITY STUDIES)
• Intestinal Cytochrome P450 and Response to Rifampicin in Rabbits
• Thirteen-week Intravenous Toxicity Study of a Novel Humanized Anti-Human Death Receptor 5 Monoclonal Antibody, CS-1008, in Cynomolgus Monkeys

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