Establishment of in vitro system for prediction of oral bioavailability in human based on species differences in oral drug absorption kinetics

• Project/Area Number: 24790177
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Setsunan University
• Principal Investigator: MASAOKA YOSHIE 摂南大学, 薬学部, 助手 (00351685)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 消化管吸収 / 摘出腸管 / 種差 / トランスポーター / 代謝酵素 / 摘出腸管膜

Research Abstract

Species differences in the first pass metabolism in the gastrointestine and the intestinal membeane permeation including the active transport of drugs make difficult to predict the human oral bioavailability accurately based on the results of in vivo animal study. We have tried to use isolated intestinal membrane to prediction of human bioavailability. By using in vitro permeation study across the isolated tissue, intestinal metabolism, P-glycoprotein mediated transport during the membrane permeation process, and then, species differences in intestinal drug absorption could be assessed quantitatively.