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Rate-limited steps of human oral absorption and QSAR studies.

Zhao, YH; Abraham, MH; Le, J; Hersey, A; Luscombe, CN; Beck, G; Sherborne, B; (2002) Rate-limited steps of human oral absorption and QSAR studies. Pharm Res , 19 (10) pp. 1446-1457.

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Abstract

PURPOSE: To classify the dissolution and diffusion rate-limited drugs and establish quantitative relationships between absorption and molecular descriptors. METHODS: Absorption consists of kinetic transit processes in which dissolution, diffusion, or perfusion processes can become the rate-limited step. The absorption data of 238 drugs have been classified into either dissolution or diffusion rate-limited based on an equilibrium method developed from solubility, dose, and percentage of absorption. A nonlinear absorption model derived from first-order kinetics has been developed to identify the relationship between percentage of drug absorption and molecular descriptors. RESULTS: Regression analysis was performed between percentage of absorption and molecular descriptors. The descriptors used were ClogP, molecular polar surface area, the number of hydrogen-bonding acceptors and donors, and Abraham descriptors. Good relationships were found between absorption and Abraham descriptors or ClogP. CONCLUSIONS: The absorption models can predict the following three BCS (Biopharmaceutics Classification Scheme) classes of compounds: class I, high solubility and high permeability; class III, high solubility and low permeability; class IV, low solubility and low permeability. The absorption models overpredict the absorption of class II, low solubility and high permeability compounds because dissolution is the rate-limited step of absorption.

Type: Article
Title: Rate-limited steps of human oral absorption and QSAR studies.
Location: United States
Keywords: Administration, Oral, Humans, Intestinal Absorption, Pharmaceutical Preparations, Quantitative Structure-Activity Relationship, Regression Analysis
UCL classification: UCL > School of BEAMS > Faculty of Maths and Physical Sciences
UCL > School of BEAMS > Faculty of Maths and Physical Sciences > Chemistry
URI: http://discovery.ucl.ac.uk/id/eprint/29676
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