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Updated: May 31, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Correlation between the systemic clearance of drugs and their food effects in humans
Venugopal P Marasanapalle1, Ramesh R Boinpally, Haijian Zhu
1Exploratory Pharmaceutics, Forest Research Institute, Farmingdale, NY 11735, USA.
Context:
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.
Conclusion:
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.
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