Improvement of inflammatory bowel diseases based on expression and functional changes of P-glycoprotein by methylpredonislone and essential fatty acids

• Project/Area Number: 21590182
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: HAYASHI Masahiro 東京薬科大学, 薬学部, 教授 (20012669)
• Co-Investigator(Kenkyū-buntansha): TOMITA Mikio 東京薬科大学, 薬学部, 准教授 (60207610)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 炎症性腸疾患 / methylpredonisolone / P-glycoprotein / 薬物療法 / 栄養療法 / 必須不飽和脂肪 / Dextran Sodium Sulfate / P-glycoproein / 必須不飽和脂肪酸 / Dextran sodium sulfate / Methylprednisolone

Research Abstract

Linoleic acid(LA) and.-linolenic acid(α-LnA) decrease the absorption of methylpredonisolone(MP) from small intestine in inflammatory bowel disease(IBD) model rats and have delivery effects to large intestine to MP. LA and α-LnA have anti-inflammatory effects and regulatory effects on expression and function of P-glycoprotein(P-gp) in intestinal epithelial cells. It suggests that administration of these essential unsaturated fatty acids not only prevent progress of IBD and also normalize intestinal absorption and disposition of the drug which is a substrate of P-gp in vivo. More experimental information and data are necessary for more efficient administration schedule of drugs in IBD therapy.

Research Products

• [Journal Article] Changes in protein and mRNA expression levels of claudin family after mucosal lesion by intestinal ischemia/reperfusion (2012)
  • Author(s): Y. Takizawa, H. Kishimoto, T. Kitazato, M. Tomita and M. Hayashi
  • Journal Title: Int. J. Pharm. Volume: 426 Pages: 82-89
  • Peer Reviewed
• [Journal Article] Nonlinear intestinal absorption of fluorescein isothiocyanate dextran 4, 000 caused by absorptive and secretory transporting system (2011)
  • Author(s): M. Tomita, R. Ohkubo, S. Ouchi, C. Kawahata and M. Hayashi
  • Journal Title: Pharmacol. Pharm. Volume: 2 Pages: 173-179
  • Peer Reviewed
• [Journal Article] Changes in the pharmacokinetics of rhodamine123 and bromosulfophtalein in rats treated with lipopolysaccharide (2011)
  • Author(s): M. Tomita, M. Hatanaka, M. Nakaike, T. Kai, C. Kobayashi, H. Murata, A. Tanaka, A. Kanbayashi and M. Hayashi
  • Journal Title: Organ Biol. Volume: 18 Pages: 145-150
  • Peer Reviewed
• [Journal Article] Absorption enhancement of acylcarnitine through changes in tight junction protein in Caco-2 Cell monolayers (2011)
  • Author(s): N.Doi, M.Tomita, M.Hayashi
  • Journal Title: Drug Metab.Pharmacokinet. Volume: 26(2) Issue: 3 Pages: 162-170
  • DOI: 10.1016/j.ejps.2010.11.016
  • Peer Reviewed
• [Journal Article] Effects of antioxidants on the ischemia/reperfusion injury in rat (2011)
  • Author(s): Y.Takizawa, H.Kishimoto, T.Kitazato, M.Tomita, M.Hayashi
  • Journal Title: Eur.J.Drug Metab.Pharmacokinet. Volume: 35 Issue: 3-4 Pages: 89-95
  • DOI: 10.1007/s13318-010-0020-y
  • Peer Reviewed
• [Journal Article] Effect of aminoguanidine on ischemia/reperfusion injury in rat small intestine (2011)
  • Author(s): Y.Takizawa, H.Kishimoto, T.Kitazato, M.Tomita, M.Hayashi
  • Journal Title: Biol.Pharm.Bull. Volume: 34(11) Pages: 1737-1743
  • NAID: 130001252858
  • Peer Reviewed
• [Journal Article] Effects of acylcarnitines on efflux transporting system in Caco-2 cell monolayers (2010)
  • Author(s): M.Tomita, M.Hayashi, et al
  • Journal Title: Eur.J.Drug Metab.Pharmacokinet. Volume: 35 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Effect of lipopolysaccharide on P-glycoprotein-mediated intestinal and biliary excretion of rhodamine123 in rats (2010)
  • Author(s): M.Tomita, M.Hayashi, et al
  • Journal Title: Int.J.Pharm. Volume: 392 Pages: 35-41
  • Peer Reviewed
• [Journal Article] Regional difference of drug permeability in the rat intestine, determined using markers of the paracellular, transcellular and some transporter routes (2010)
  • Author(s): M.Tomita, M.Hayashi, et al
  • Journal Title: Organ Biol. Volume: 17 Pages: 77-87
  • Peer Reviewed
• [Journal Article] Nonlinear intestinal absorption of methylprednisolone caused by absorptive and secretory transporters (2010)
  • Author(s): M.Tomita, M.Hayashi, et al.
  • Journal Title: International Journal Pharmaceutics 387 Pages: 1-6
  • Peer Reviewed
• [Presentation] Enhancing mechanism of drug absorption by acylcarnitines (2012)
  • Author(s): N. Doi, A. Kimura, M. Tomita and M. Hayashi
  • Organizer: International Symposium on Past, Present and Future of Molecular Pharmacokinetics
  • Place of Presentation: Hitotsubashi Hall(Tokyo, Japan)
  • Year and Date: 2012-01-16
• [Presentation] 腸管におけるアシルカルニチンの吸収促進剤としての有用性と安全性 (2011)
  • Author(s): 土井信幸、富田幹雄、木村あおい、林正弘
  • Organizer: 日本薬物動態学会第26回年会
  • Place of Presentation: 広島国際会議場(広島)
  • Year and Date: 2011-11-16
• [Presentation] Acylcarnitines as useful absorption enhancer in clinical use (2011)
  • Author(s): N. Doi, M. Tomita, A. Kimura and M. Hayashi
  • Organizer: International Symposium on BA/BE of Oral Drug Products
  • Place of Presentation: Kobe International conference center(Kobe, Japan)
  • Year and Date: 2011-06-29
• [Presentation] アシルカルニチンによるTight JunctionおよびABCトランスポーター機能変化における濃度依存性と寄与率の変動 (2011)
  • Author(s): 木村あおい、富田幹雄、土井信幸、新井友里、吉田未紀、林正弘
  • Organizer: 日本薬剤学会第26回年会
  • Place of Presentation: タワーホール船堀(東京)
  • Year and Date: 2011-05-29
• [Presentation] アシルカルニチンの吸収促進作用の腸管部位差 (2011)
  • Author(s): 土井信幸、富田幹雄、木村あおい、林正弘
  • Organizer: 日本薬剤学会第26回年会
  • Place of Presentation: タワーホール船堀(東京)
  • Year and Date: 2011-05-29