Bioavailability Research Project, Formulation Research Institute, Otsuka Pharmaceutical Co. Ltd., 224-18 Ebisuno Hiraishi Kawauchi-cho, Tokushima 771-0182, Japan.
Department of Drug Metabolism and Pharmacokinetics, Drug Safety Research Center, Tokushima Research Institute, Otsuka Pharmaceutical Co. Ltd., 460-10 Kagasuno Kawauchi-cho, Tokushima 771-0192, Japan.
Eur J Pharm Biopharm. 2018 Jan;122:49-53. doi: 10.1016/j.ejpb.2017.09.015. Epub 2017 Sep 30.
The purpose of this study was to evaluate the intestinal metabolism and absorption in a mini-Ussing chamber equipped with animal intestinal tissues, based on the transport index (TI). TI value was defined as the sum of drug amounts transported to the basal-side component (X) and drug amounts accumulated in the tissue (T), which are normalized by AUC of a drug in the apical compartment, as an index for drug absorption. Midazolam was used as a test compound for the evaluation of intestinal metabolism and absorption. The metabolite formulation of midazolam was observed in both rats and dogs. Ketoconazole inhibited the intestinal metabolism of midazolam in rats and improved its intestinal absorption to a statistically significant extent. Therefore, the mini-Ussing chamber, equipped with animal intestinal tissues, showed potential to use the evaluation of the intestinal metabolism and absorption, including the assessment of species differences.
本研究旨在通过转运指数 (TI) 评估配备动物肠组织的迷你 Ussing 室中的肠道代谢和吸收。TI 值定义为输送到基底侧成分 (X) 的药物量与组织中累积的药物量 (T) 之和，通过药物在腔室中的 AUC 归一化，作为药物吸收的指标。咪达唑仑被用作评估肠道代谢和吸收的测试化合物。咪达唑仑的代谢产物形式在大鼠和狗中均有观察到。酮康唑抑制了大鼠中咪达唑仑的肠道代谢，并在统计学上显著改善了其肠道吸收。因此，配备动物肠组织的迷你 Ussing 室具有评估肠道代谢和吸收的潜力，包括评估物种差异。
