Analysis of drug absorption behavior under gastrointestintestinal diseases related with abnormal metabolism of serotonin

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460197
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Okayama University
• Principal Investigator: Higaki Kazutaka 岡山大学, 医歯薬学総合研究科, 教授 (60284080)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 腸神経系 / セロトニン枯渇 / 経口吸収挙動 / 有機アニオン系化合物 / 消化管内移行速度 / bioavailability / 非線形性 / GITA model

Outline of Final Research Achievements

It is known that 5-HT regulating the gastrointestinal (GI) motility and function is deeply related with several serious GI diseases such as irritable bowel syndrome. In this study, we examined the effect of 5-HT depletion on oral absorption of an organic anion drug by utilizing phenol red (PR) as a model drug. 5-HT depletion significantly decreased PR absorption at low dose of PR, but tended to increase it at its high dose. The enhancement of luminal secretion by Mrp2 and BCRP induced by 5-HT depletion and it functional saturation, and the change in permeability via passive diffusion would be responsible for the dose-dependent difference for the effect of 5-HT depletion on PR absorption. Furthermore, 5-HT depletion accelerated GI-transit at upper segments, but suppressed it at lower segments, suggesting that the sequential propagation of GI- motility from proximal to distal segments was disordered.

Free Research Field

医歯薬学