Research Articles
Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure–activity relationship (QSAR) with the Abraham descriptors

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Abstract

The human intestinal absorption of 241 drugs was evaluated. Three main methods were used to determine the human intestinal absorption: bioavailability, percentage of urinary excretion of drug‐related material following oral administration, and the ratio of cumulative urinary excretion of drug‐related material following oral and intravenous administration. The general solvation equation developed by Abraham's group was used to model the human intestinal absorption data of 169 drugs we considered to have reliable data. The model contains five Abraham descriptors calculated by the ABSOLV program. The results show that Abraham descriptors can successfully predict human intestinal absorption if the human absorption data is carefully classified based on solubility and administration dose to humans. © 2001 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:749–784, 2001

Section snippets

INTRODUCTION

The prediction of human intestinal absorption is a major goal in the design, optimization, and selection of candidates for the development of oral drugs. The focus of modern drug discovery is now not simply on the pharmacological activity, but also on seeking favorable absorption, distribution, metabolism, and excretion properties.1, 2, 3, 4 The growth in drug discovery of combinatorial chemistry methods, where large numbers of candidate compounds are synthesized and screened in parallel for in

Human Intestinal Absorption Data

The names of drug and drug‐like compounds and related data are listed in Table 1 and 2. The absorption data was collected and evaluated from 244 papers.1, 2, 3, 4, 5, 8, 9, 10, 11, 12, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 52, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96

Evaluation of Human Intestinal Absorption Data

Drug absorption is a complex process that is dependent on numerous biochemical, physiological, and physicochemical factors. In a thorough review of the subject, Sietsema 263 accurately points out that the terms absorption and bioavailability are often incorrectly and interchangeably used. Sietsema defined absorption as “the drug passing from the lumen of the gastrointestinal (GI) tract into the tissue of the GI tract. Once in the tissue, the drug is considered absorbed”.

Surveying the papers, it

Acknowledgements

Y. H. Zhao and J. Le are grateful to Glaxo Wellcome and Roche Products Ltd. for a postdoctoral research fellowship and a research studentship.

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