Document Detail


Predicting effect of food on extent of drug absorption based on physicochemical properties.
MedLine Citation:
PMID:  17385020     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To develop a statistical model for predicting effect of food on the extent of absorption (area under the curve of time-plasma concentration profile, AUC) of drugs based on physicochemical properties. MATERIALS AND METHODS: Logistic regression was applied to establish the relationship between the effect of food (positive, negative or no effect) on AUC of 92 entries and physicochemical parameters, including clinical doses used in the food effect study, solubility (pH 7), dose number (dose/solubility at pH 7), calculated Log D (pH 7), polar surface area, total surface area, percent polar surface area, number of hydrogen bond donor, number of hydrogen bond acceptors, and maximum absorbable dose (MAD). RESULTS: For compounds with MAD >or= clinical dose, the food effect can be predicted from the dose number category and Log D category, while for compounds with MAD < clinical dose, the food effect can be predicted from the dose number category alone. With cross validation, 74 out of 92 entries (80%) were predicted into the correct category. The correct predictions were 97, 79 and 68% for compounds with positive, negative and no food effect, respectively. CONCLUSIONS: A logistic regression model based on dose, solubility, and permeability of compounds is developed to predict the food effect on AUC. Statistically, solubilization effect of food primarily accounted for the positive food effect on absorption while interference of food with absorption caused negative effect on absorption of compounds that are highly hydrophilic and probably with narrow window of absorption.
Authors:
Chong-Hui Gu; Hua Li; Jaquan Levons; Kimberley Lentz; Rajesh B Gandhi; Krishnaswamy Raghavan; Ronald L Smith
Publication Detail:
Type:  Journal Article     Date:  2007-03-24
Journal Detail:
Title:  Pharmaceutical research     Volume:  24     ISSN:  0724-8741     ISO Abbreviation:  Pharm. Res.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-21     Completed Date:  2007-08-09     Revised Date:  2008-06-05    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1118-30     Citation Subset:  IM    
Affiliation:
Biopharmaceutics R&D, Bristol-Myers Squibb Co., New Brunswick, New Jersey, USA. chong-hui_gu@vrtx.com
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Area Under Curve
Food-Drug Interactions*
Pharmacokinetics*
Comments/Corrections
Erratum In:
Pharm Res. 2008 Apr;25(4):979

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Accumulation of succinimide in a recombinant monoclonal antibody in mildly acidic buffers under elev...
Next Document:  Effect of solid lipid nanoparticles formulation compositions on their size, zeta potential and poten...