Intestinal Cytochrome P450 and Response to Rifampicin in Rabbits.

• Nakamura Takahiro

  Drug Metabolism and Molecular Toxicology,Graduate School of Pharmaceutical Sciences,Tohoku University,Aramaki,Aoba-ku,Sendai 980-8578,Japan

• Okada Keizo

  Drug Metabolism and Molecular Toxicology,Graduate School of Pharmaceutical Sciences,Tohoku University,Aramaki,Aoba-ku,Sendai 980-8578,Japan

• Nagata Kiyoshi

  Drug Metabolism and Molecular Toxicology,Graduate School of Pharmaceutical Sciences,Tohoku University,Aramaki,Aoba-ku,Sendai 980-8578,Japan

• Yamazoe Yasushi

  Drug Metabolism and Molecular Toxicology,Graduate School of Pharmaceutical Sciences,Tohoku University,Aramaki,Aoba-ku,Sendai 980-8578,Japan

Abstract

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.

Journal

• The Japanese Journal of Pharmacology

  The Japanese Journal of Pharmacology 82 (3), 232-239, 2000

  The Japanese Pharmacological Society

Keywords

• Cytochrome P450
• Intestinal mucosa
• Rifampicin
• Induction
• Testosterone 6β-hydroxylation

Details

• CRID: 1390001204284899072
• NII Article ID: 10008183542
• NII Book ID: AA00691188
• DOI: 10.1254/jjp.82.232
• COI: 1:CAS:528:DC%2BD3cXitFOiurY%3D
• ISSN: 13473506
• ISSN: 00215198
• NDL BIB ID: 5321051
• PubMed: 10887954
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I5321051
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819306894?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819306894?httpAccept=text/plain
• Web Site: https://www.jstage.jst.go.jp/article/jjp/82/3/82_3_232/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2000163650
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• Abstract License Flag: Disallowed