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

Research output: Contribution to journalArticle

12 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 - 2013 Aug

Fingerprint

Intestinal Absorption
Pharmaceutical Preparations
Metoprolol
Atenolol
Ulcerative Colitis
Crohn Disease
Permeability

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Miyake, M., Toguchi, H., Nishibayashi, T., Higaki, K., Sugita, A., Koganei, K., ... 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

Establishment of novel prediction system of intestinal absorption in humans using human intestinal tissues. / Miyake, Masateru; Toguchi, Hajime; Nishibayashi, Toru; Higaki, Kazutaka; Sugita, Akira; Koganei, Kazutaka; Kamada, Nobuhiko; Kitazume, Mina T.; Hisamatsu, Tadakazu; Sato, Toshiro; Okamoto, Susumu; Kanai, Takanori; Hibi, Toshifumi.

In: Journal of Pharmaceutical Sciences, Vol. 102, No. 8, 08.2013, p. 2564-2571.

Research output: Contribution to journalArticle

Miyake, M, Toguchi, H, Nishibayashi, T, Higaki, K, Sugita, A, Koganei, K, Kamada, N, Kitazume, MT, 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, vol. 102, no. 8, pp. 2564-2571. https://doi.org/10.1002/jps.23609
Miyake, Masateru ; Toguchi, Hajime ; Nishibayashi, Toru ; Higaki, Kazutaka ; Sugita, Akira ; Koganei, Kazutaka ; Kamada, Nobuhiko ; Kitazume, Mina T. ; Hisamatsu, Tadakazu ; Sato, Toshiro ; Okamoto, Susumu ; Kanai, Takanori ; Hibi, Toshifumi. / Establishment of novel prediction system of intestinal absorption in humans using human intestinal tissues. In: Journal of Pharmaceutical Sciences. 2013 ; Vol. 102, No. 8. pp. 2564-2571.
@article{8da41b4ec1f5495c9910b5fc00af2124,
title = "Establishment of novel prediction system of intestinal absorption in humans using human intestinal tissues",
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.",
keywords = "Human absorption, Human tissues, Mini-Ussing chamber, Prediction, Transport index (TI)",
author = "Masateru Miyake and Hajime Toguchi and Toru Nishibayashi and Kazutaka Higaki and Akira Sugita and Kazutaka Koganei and Nobuhiko Kamada and Kitazume, {Mina T.} and Tadakazu Hisamatsu and Toshiro Sato and Susumu Okamoto and Takanori Kanai and Toshifumi Hibi",
year = "2013",
month = "8",
doi = "10.1002/jps.23609",
language = "English",
volume = "102",
pages = "2564--2571",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "John Wiley and Sons Inc.",
number = "8",

}

TY - JOUR

T1 - Establishment of novel prediction system of intestinal absorption in humans using human intestinal tissues

AU - Miyake, Masateru

AU - Toguchi, Hajime

AU - Nishibayashi, Toru

AU - Higaki, Kazutaka

AU - Sugita, Akira

AU - Koganei, Kazutaka

AU - Kamada, Nobuhiko

AU - Kitazume, Mina T.

AU - Hisamatsu, Tadakazu

AU - Sato, Toshiro

AU - Okamoto, Susumu

AU - Kanai, Takanori

AU - Hibi, Toshifumi

PY - 2013/8

Y1 - 2013/8

N2 - 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.

AB - 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.

KW - Human absorption

KW - Human tissues

KW - Mini-Ussing chamber

KW - Prediction

KW - Transport index (TI)

UR - http://www.scopus.com/inward/record.url?scp=84881027940&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881027940&partnerID=8YFLogxK

U2 - 10.1002/jps.23609

DO - 10.1002/jps.23609

M3 - Article

VL - 102

SP - 2564

EP - 2571

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 8

ER -