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Cited by 132Drug Solubulity and Delivery SystemsDrug Transport and Resistance MechanismsPharmacogenetics and Drug Metabolism

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Evaluation of a single-pass intestinal-perfusion method in rat for the prediction of absorption in man

Salphati, Laurent, Childers, Kelly, Pan, Lin, Tsutsui, Ken, Takahashi, Lori·2001·Journal of Pharmacy and Pharmacology
DOI 10.1211/0022357011776252
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Abstract

Prediction of the fraction of dose absorbed from the intestine (Fa) in man is essential in the early drug discovery stage. In-vitro assays in Caco-2 and MDCK cells are routinely used for that purpose, and their predictive value has been reported. However, in-situ techniques might provide a more accurate estimation of Fa. In this study, we evaluated a single-pass intestinal-perfusion (SPIP) method in the rat for its use in the prediction of absorption in man and compared it with a previous report using cell-based assays. Effective permeability coefficients (Peff) were determined in rats for 14 compounds, and ranged from 0.043 times 10−4 cm s−1 to 1.67 times 10−4 cms−1. These values strongly correlated (r2 = 0.88) with reported Peff values for man. In addition, the Spearman rank correlation coefficient calculated for in-situ-derived Peff and absorption in man was 0.92 while for the previously tested in-vitro Caco-2 and MDCK systems vs absorption in man, the correlation coefficients were 0.61 and 0.59, respectively. SPIP provided a better prediction of human absorption than the cell-based assays. This method, although time consuming, could be used as a secondary test for studying the mechanisms governing the absorption of new compounds, and for predicting more accurately the fraction absorbed in man.

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Metadata

Authors
Salphati, L., Childers, K., Pan, L., Tsutsui, K., & Takahashi, L.
Affiliations
Affymax (United States) (US)
Corresponding author
Salphati, Laurent
ORCID
Pan, Lin
Venue
Journal of Pharmacy and Pharmacology
Publisher
Oxford University Press (OUP)
Published
2001-07-01
Volume
53
Issue
7
Pages
1007-1013
ISSN
  • 0022-3573 (ISSN-L)
  • 2042-7158
DOI
10.1211/0022357011776252
OpenAlex
W2080158345
Cited by
132
References
1
Citations by year
2026: 2 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 6 · 2020: 3 · 2019: 1 · 2018: 9 · 2017: 12 · 2016: 8 · 2015: 7 · 2014: 6 · 2013: 10 · 2012: 10
FWCI
2.12
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Journal of Pharmacy and Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
single-pass intestinal perfusion, fraction absorbed, effective permeability, rat model, Caco-2 cells, MDCK cells, drug absorption
MeSH terms
Animals, Cell Line, Cell Membrane Permeability, Humans, Ileum, Intestinal Absorption, Male, Perfusion, Predictive Value of Tests, Rats, Sprague-Dawley, Caco-2 Cells, Rats

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