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2002 Fiscal Year Final Research Report Summary

Pharmacokinetic and Cellular Biological Study on Colonic Absorption : Strategies for Optimized Controlled Release Oral Drug Delivery

Research Project

Project/Area Number 12672155
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 医薬分子機能学
Research InstitutionNagoya City University

Principal Investigator

YUASA Hiroaki  Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (20191471)

Co-Investigator(Kenkyū-buntansha) INOUE Katsuhisa  Graduate School of Pharmaceutical Sciences, Assistant Professor, 大学院・薬学研究科, 講師 (50315892)
HAYASHI Yayoi  Graduate School of Pharmaceutical Sciences, Assistant Professor, 大学院・薬学研究科, 講師 (00117847)
Project Period (FY) 2000 – 2002
Keywordscolon / small intestine / carrier-mediated transport / first-pass metabolism / riboflavin / cyclosporine / CYP3A / P-glycoprotein
Research Abstract

It was found in the rat that riboflavin transport in the colon is mediated by a Na^+dependent carrier-mediated transport system similar to one in the small intestine. The transport system in the colon was as efficient as one in the small intestine. It was also found that several tricyclic-type drugs analogous to riboflavin, such as chlorpromazine, specifically inhibit carrier-mediated riboflavin transport in both intestinal sites. Those inhibitors may include competitive substrates that could be transported, though it requires more detailed investigation. Furthermore, the riboflavin transport systems in both intestinal sites seemed to be quite similar in terms of recognition of substrates and inhibitors, though they might not be identical. For some other carrier-mediated transport systems examined, those of D-glucose and bile acids were found to be present in the colon, though far less efficient than the riboflavin transport system. Thus, the riboflavin transport system seemed to be most promising for utilization in oral drug delivery via colon. Drugs designed to fit the riboflavin carriers and as well absorbed from the colon as from the small intestine would be suitable for a sustained-release formulation that is effective even after reaching the colon.
Drugs that are metabolized by CYP3A, such as cyclosporine, were found to be significantly metabolized at first-pass in the colon of rats as well as in the small intestine. Thus, in terms of metabolism by CYP3A, delivery via colon would not lead to any further reduction in bioavailability, compared with delivery via small intestine. However, the membrane permeability of cyclosporine, which is restricted by secretory transport by P-glycoprotein, was significantly lower in the colon than in the small intestine. Therefore, for those that undergo CYP3A metabolism and P-glycoprotein secretion, delivery via colon could lead to a reduction in the bioavailability.

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Yuasa, H. et al.: "Carrier-mediated transport of riboflavin in the rat colon"Biopharm. Drag Dispos.. 21. 77-82 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tomei et al.: "Transport functions of riboflavin carriers in the rat small intestine and colon : roles in drug absorption"Drug Delivery. 8. 119-124 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 岩尾岳洋他: "ラット小腸におけるnifedipineの初回通過代謝の評価"薬物動態. 16. S190 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中島亜起他: "ラット腸管におけるビオチン輸送担体の機能解析"薬剤学. 62. S166 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 岩尾岳洋他: "ラット小腸におけるニフェジピンの初回通過代謝"薬剤学. 62. S181 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鎌倉康隆他: "ラット腸管からのシクロスポリンのバイオアベイラビリティーの投与部位差"薬剤学. 62. S242 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwao, T. et al.: "Metabolic extraction of nifedipine during absorption from the rat small intestine"Drug Metab. Pharmacokin. 17. 546-553 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tomei, S. et al.: "Search for carrier-mediated transport systems in the rat colon"Biol. Pharm. Bull.. 26. 274-277 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tomei, S. et al.: "Kinetic characterization of carrier-mediated transport systems for D-glucose and taurocholate in the everted sacs of the rat colon"Biol. Pharm. Bull.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuasa, H., Hirobe, M., Tomei, S. and Watanabe, J.: "Carrier-mediated transport of riboflavin in the rat colon"Biopharm. Drug Dispos.. 21-2. 77-82 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tomei, S., Yuasa, H., Inoue, K. and Watanabe, J.: "Transport functions of riboflavin carriers in the rat small intestine and colon : roles in drug absorption"Drug Delivery. 8-3. 119-124 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwao, T., Inoue, K., Hayashi, Y., Yuasa, H. and Watanabe, J.: "Evaluation of first-pass metabolism of nifedipine in the rat small intestine."Xenobio. Metabol. Dispos.. 16-S. S190 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima, A., Inoue, K., Hayashi, Y. and Yuasa, H.: "Functional analysis of the biotin carrier in the rat intestine"J. Pharm. Sci. Technol.. 62-S. S166 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwao, T., Inoue, K., Hayashi, Y., Yuasa, H. and Watanabe, J.: "First-pass metabolism of nifedipine in the rat small intestine"J. Pharm. Sci. Technol.. 62-S. S181 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kamakura, Y., Inoue, K., Hayashi, Y. and Yuasa, H.: "Site-dependent bioavailability of cyclosporine from the rat intestine"J. Pharm. Sci. Technol.. 62-S. S242 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwao, T., Inoue, K., Hayashi, Y., Yuasa, H. and Watanabe, J.: "Metabolic extraction of nifedipine during absorption from the rat small intestine"Drug Metab. Pharmacokin. 17-6. 546-553 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tomei, S., Hayashi, Y., Inoue, K., Torimoto, M., Ota, Y., Morita, K., Yuasa, H. and Watanabe, J.: "Search for carrier-mediated transport systems in the rat colon"Biol. Pharm. Bull.. 26-2. 274-277 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tomei, S., Torimoto, M., Hayashi, Y., Inoue, K., Yuasa, H. and Watanabe, J.: "Kinetic characterization of carrier-mediated transport systems for D-glucose and taurocholate in the everted sacs of the rat colon"Biol. Pharm. Bull.. in press.

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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