Regional intestinal drug permeation: Biopharmaceutics and drug development

Lennernäs, Hans

doi:10.1016/j.ejps.2013.08.025

Cited by 103Drug Solubulity and Delivery SystemsAdvanced Drug Delivery SystemsDrug Transport and Resistance Mechanisms

Regional intestinal drug permeation: Biopharmaceutics and drug development

Lennernäs, Hans·2014·European Journal of Pharmaceutical Sciences

DOI 10.1016/j.ejps.2013.08.025

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Abstract

Over the last 25 years, profound changes have been seen in both the development and regulation of pharmaceutical dosage forms, due primarily to the extensive use of the biopharmaceutical classification system (BCS) in both academia and industry. The BCS and the FDA scale-up and post-approval change guidelines were both developed during the 1990s and both are currently widely used to claim biowaivers. The development of the BCS and its wide acceptance were important steps in pharmaceutical science that contributed to the more rational development of oral dosage forms. The effective permeation (Peff) of drugs through the intestine often depends on the combined outcomes of passive diffusion and multiple parallel transport processes. Site-specific jejunal Peff cannot reflect the permeability of the whole intestinal tract, since this varies along the length of the intestine, but is a useful approximation of the fraction of the oral dose that is absorbed. It appears that drugs with a jejunal Peff>1.5×10(-4)cm/s will be completely absorbed no matter which transport mechanisms are utilized. In this paper, historical clinical data originating from earlier open, single-pass perfusion studies have been used to calculate the Peff of different substances from sites in the jejunum and ileum. More exploratory in vivo studies are required in order to obtain reliable data on regional intestinal drug absorption. The development of experimental and theoretical methods of assessing drug absorption from both small intestine and various sites in the colon is encouraged. Some of the existing human in vivo data are discussed in relation to commonly used cell culture models. It is crucial to accurately determine the input parameters, such as the regional intestinal Peff, as these will form the basis for the expected increase in modeling and simulation of all the processes involved in GI drug absorption, thus facilitating successful pharmaceutical development in the future. It is suggested that it would be feasible to use open, single-pass perfusion studies for the in vivo estimation of regional intestinal Peff, but that care should be taken in the study design to optimize the absorption conditions.

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There is considerable uncertainty and ongoing debate over the relevant parameterisation of intestinal water volumes and the parameterisation of the colonic model compartments is uncertain.
“there is considerable uncertainty and ongoing debate over the relevant parameterisation of intestinal water volumes [71-73] and the parameterisation of the colonic model compartments is uncertain [74].”
From Physiologically Based Pharmacokinetic Modelling for First-In-Human Predictions: An Updated Model Building Strategy Illustrated with Challenging Industry Case Studies (2019) · cites this paper as [74]

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Authors: Lennernäs, H.
Affiliations: Uppsala University (SE)
Corresponding author: Lennernäs, Hans
ORCID: Lennernäs, Hans
Venue: European Journal of Pharmaceutical Sciences
Publisher: Elsevier BV
Published: 2014-06
Volume: 57
Pages: 333-341
ISSN: 0928-0987 (ISSN-L)
DOI: 10.1016/j.ejps.2013.08.025
OpenAlex: W2013095023
Cited by: 103
References: 94
Citations by year: 2026: 7 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 9 · 2021: 8 · 2020: 11 · 2019: 8 · 2018: 11 · 2017: 14 · 2016: 6 · 2015: 12 · 2014: 4 · 2013: 1
FWCI: 0.97
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: European Journal of Pharmaceutical Sciences (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords: effective permeability, biowaiver, Biopharmaceutics Classification System, single-pass perfusion, oral drug absorption, passive diffusion, drug transport mechanisms, cell culture model
MeSH terms: Administration, Oral, Biological Availability, Biopharmaceutics, Dosage Forms, Pharmaceutical Preparations, Humans, Intestinal Absorption, Intestinal Mucosa, Models, Biological, Permeability, Pharmacokinetics, Solubility, Drug Discovery

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Regional intestinal drug permeation: Biopharmaceutics and drug development

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