Cited by 304Drug Solubulity and Delivery SystemsDrug Transport and Resistance MechanismsBarrier Structure and Function Studies

Intestinal permeability and its relevance for absorption and elimination

Lennernäs, H.·2007·Xenobiotica

Abstract

Human jejunal permeability (P(eff)) is determined in the intestinal region with the highest expression of carrier proteins and largest surface area. Intestinal P(eff) are often based on multiple parallel transport processes. Site-specific jejunal P(eff) cannot reflect the permeability along the intestinal tract, but they are useful for approximating the fraction oral dose absorbed. It seems like drugs with a jejunal P(eff) > 1.5 x 10(-4) cm s(-1) will be completely absorbed no matter which transport mechanism(s) are utilized. Many drugs that are significantly effluxed in vitro have a rapid and complete intestinal absorption (i.e. >85%) mediated by passive transcellular diffusion. The determined jejunal P(eff) for drugs transported mainly by absorptive carriers (such as peptide and amino acid transporters) will accurately predict the fraction of the dose absorbed as a consequence of the regional expression. The data also show that: (1) the human intestinal epithelium has a large resistance towards large and hydrophilic compounds; and (2) the paracellular route has a low contribution for compounds larger than approximately molecular weight 200. There is a need for more exploratory in vivo studies to clarify drug absorption and first-pass extraction along the intestine. One is encouraged to develop in vivo perfusion techniques for more distal parts of the gastrointestinal tract in humans. This would stimulate the development of more relevant and complex in vitro absorption models and form the basis for an accurate physiologically based pharmacokinetic modelling of oral drug absorption.

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Crossref · 10.1080/00498250701704819

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Authors
Lennernäs, H.
Affiliations
Uppsala University (SE)
Corresponding author
Lennernäs, H.
Venue
Xenobiotica
Published
2007-11
Volume
37
Issue
10-11
Pages
1015-1051
ISSN
  • 0049-8254 (ISSN-L)
  • 1366-5928
OpenAlex
W2007052092
Cited by
304
References
199
Citations by year
2026: 14 · 2025: 21 · 2024: 15 · 2023: 16 · 2022: 16 · 2021: 20 · 2020: 15 · 2019: 16 · 2018: 19 · 2017: 8 · 2016: 13 · 2015: 13 · 2014: 20 · 2013: 16 · 2012: 24
FWCI
11.63
Type
journal article
Language
en
Open access
closed
Locations
  • Xenobiotica (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 › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
intestinal permeability, oral drug absorption, paracellular transport, efflux pumps, first-pass extraction, in vivo perfusion, physiologically based pharmacokinetic modelling, in vitro absorption model, human intestinal epithelium
MeSH terms
Biological Transport, Active, Carrier Proteins, Humans, Intestinal Absorption, Jejunum, Models, Biological, Permeability, Xenobiotics

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