title: Correlation between the systemic clearance of drugs and their food effects in humans.
abstract: BACKGROUND
  Food effects were defined as positive, when coadministration of food causes an increase in the extent of absorption (AUC(0-∞)) of a drug when compared with fasted state drug administration and no effect when coadministration of food causes no change in AUC(0-∞). In general, low solubility drugs exhibit positive food effects due to improved solubility in fed state administration. But, certain high-solubility and high-permeability drugs that undergo extensive presystemic metabolism exhibit positive food effects because of the increased splanchnic hepatic blood flow in the fed state presumably causing a fraction of drug to bypass first-pass metabolism during absorption.
  
  
  OBJECTIVE
  In this study, systemic clearance (Cl) of structurally diverse high-permeability and high-solubility drugs was correlated to their food effects to explore whether drugs undergoing low clearance exhibited no food effects and drugs undergoing high clearance exhibited positive food effects.
  
  
  METHODS
  Six drugs exhibiting positive food effects and nine drugs exhibiting no food effects (for comparison) were selected for linear regression analysis.
  
  
  RESULTS
  Regression analysis of the selected drugs indicated that percent food effects correlated linearly to Cl and fitted the equation: percent food effects = 0.9163 × Cl - 6.4789. The R(2), p-value and power of the regression model were >0.88, 0.9999, respectively indicating the direct correlation between Cl and food effects of the selected model drugs; other statistical tests validated the model.
  
  
  CONCLUSIONS
  The model indicated that high-solubility and high-permeability drugs undergoing Cl of more than 27 L/h may exhibit statistically significant positive food effects.
authors.affiliation: Exploratory Pharmaceutics, Forest Research Institute, Farmingdale, NY 11735, USA.
authors.forename: Venugopal P
authors.initials: VP
authors.lastname: Marasanapalle
authors.forename: Ramesh R
authors.initials: RR
authors.lastname: Boinpally
authors.forename: Haijian
authors.initials: H
authors.lastname: Zhu
authors.forename: Andreas
authors.initials: A
authors.lastname: Grill
authors.forename: Fuxing
authors.initials: F
authors.lastname: Tang
mesh_terms: D000281:Administration, Intranasal / Q000379:methods*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D002439:Cefotaxime / Q000493:pharmacokinetics*; D018565:Food-Drug Interactions / Q000502:physiology*; D006801:Humans; D008297:Male; D016920:Meningitis, Bacterial / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000900:Anti-Bacterial Agents; D002439:Cefotaxime