Rate-limited steps of human oral absorption and QSAR studies.
Pharm Res
; 19(10): 1446-57, 2002 Oct.
Article
en En
| MEDLINE
| ID: mdl-12425461
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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Preparaciones Farmacéuticas
/
Relación Estructura-Actividad Cuantitativa
/
Absorción Intestinal
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Pharm Res
Año:
2002
Tipo del documento:
Article
País de afiliación:
Reino Unido