title: Predicting effect of food on extent of drug absorption based on physicochemical properties.
abstract: OBJECTIVE
  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.
  
  
  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: Biopharmaceutics R&D, Bristol-Myers Squibb Co., New Brunswick, New Jersey, USA. chong-hui_gu@vrtx.com
authors: Chong-Hui
authors: CH
authors: Gu
authors: Hua
authors: H
authors: Li
authors: Jaquan
authors: J
authors: Levons
authors: Kimberley
authors: K
authors: Lentz
authors: Rajesh B
authors: RB
authors: Gandhi
authors: Krishnaswamy
authors: K
authors: Raghavan
authors: Ronald L
authors: RL
authors: Smith
mesh_terms: D019540:Area Under Curve; D018565:Food-Drug Interactions; D010599:Pharmacokinetics