Establishment of novel prediction system of intestinal absorption in humans using human intestinal tissues

Masateru Miyake, Hajime Toguchi, Toru Nishibayashi, Kazutaka Higaki, Akira Sugita, Kazutaka Koganei, Nobuhiko Kamada, Mina T. Kitazume, Tadakazu Hisamatsu, Toshiro Sato, Susumu Okamoto, Takanori Kanai, Toshifumi Hibi

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15 Citations (Scopus)

Abstract

The objective of this study was to establish a novel prediction system of drug absorption in humans by utilizing human intestinal tissues. Based on the transport index (TI), a newly defined parameter, calculated by taking account of the change in drug concentrations because of precipitation on the apical side and the amounts accumulated in the tissue and transported to the basal side, the absorbability of drugs in rank order as well as the fraction of dose absorbed (Fa) in humans were estimated. Human intestinal tissues taken from ulcerative colitis or Crohn's disease patients were mounted in a mini-Ussing chamber and transport studies were performed to evaluate the permeation of drugs, including FD-4, a very low permeable marker, atenolol, a low permeable marker, and metoprolol, a high permeable marker. Although apparent permeability coefficients calculated by the conventional equation did not reflect human Fa values for FD-4, atenolol, and metoprolol, TI values were well correlated with Fa values, which are described by 100 · [1 - e - f · (TI - α)]. Based on this equation, Fa values in humans for other test drugs were predicted successfully, indicating that our new system utilizing human intestinal tissues would be valuable for predicting oral drug absorption in humans.

Original languageEnglish
Pages (from-to)2564-2571
Number of pages8
JournalJournal of Pharmaceutical Sciences
Volume102
Issue number8
DOIs
Publication statusPublished - Aug 2013

Keywords

  • Human absorption
  • Human tissues
  • Mini-Ussing chamber
  • Prediction
  • Transport index (TI)

ASJC Scopus subject areas

  • Pharmaceutical Science

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    Miyake, M., Toguchi, H., Nishibayashi, T., Higaki, K., Sugita, A., Koganei, K., Kamada, N., Kitazume, M. T., Hisamatsu, T., Sato, T., Okamoto, S., Kanai, T., & Hibi, T. (2013). Establishment of novel prediction system of intestinal absorption in humans using human intestinal tissues. Journal of Pharmaceutical Sciences, 102(8), 2564-2571. https://doi.org/10.1002/jps.23609