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Towards Quantitative Prediction of Oral Drug Absorption

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Abstract

Although several routes of administration can be considered for new drug entities, the oral route remains the most popular. To predict the in vivo performance of a drug after oral administration from in vitro data, it is essential that the factors limiting absorption can be modelled. Factors limiting oral drug absorption are typically slow and/or incomplete dissolution, formation of insoluble complexes and/or decomposition in the gastrointestinal lumen, poor net permeability and first-pass metabolism. Although many attempts have been made to make global forecasts of oral bioavailability based on a single parameter (ranging from the partition coefficient [logP] to the polar surface area), it is clear from the diversity of properties that can influence delivery of drugs via the oral route that such an approach can at best lead to a qualitative estimation. To predict in vivo performance in a more quantitative way, it is instead necessary to identify the extent to which each of the aforementioned factors can limit absorption, and then combine the information into a comprehensive model of the absorptive processes. Much progress has been made in the last 10 years on developing methods to pin down the extent to which each of the factors actually limits the absorption of a given compound and, concomitantly, physiological models have been evolved, which show promise in terms of being able to integrate the information generated about each of the individual limiting factors. This article attempts to summarize recent progress on the various fronts as a kind of ‘progress report’ towards quantitative prediction of oral drug absorption.

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Acknowledgements

Kirsten Thelan is financially supported by Bayer Technology Services GmbH (Leverkusen, Germany) and Ekarat Jantratid by F. Hoffmann La Roche (Nutley, NJ, USA). No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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  1. Institute of Pharmaceutical Technology, Goethe University, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany

    Jennifer B. Dressman, Kirstin Thelen & Ekarat Jantratid

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Dressman, J.B., Thelen, K. & Jantratid, E. Towards Quantitative Prediction of Oral Drug Absorption. Clin Pharmacokinet 47, 655–667 (2008). https://doi.org/10.2165/00003088-200847100-00003

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