Abstract
BackgroundFood is known to affect drug absorption by delaying gastric emptying time, altering gastrointestinal pH, stimulating bile flow, increasing splanchnic blood flow, or physically interacting with drugs. Although food is known to affect the pharmacokinetics of oral antineoplastic drugs, the relationship between the effects of food and the physicochemical properties of drugs remains unclear.MethodsIn this study, we surveyed the literature on three kinds of pharmacokinetic changes, AUC ratio, Cmax ratio and Tmax ratio, in the fasted and fed state for 72 oral antineoplastic drugs that were listed on the drug price standard in May 2018 in Japan. We further predicted the physicochemical properties from the 2D chemical structure of the antineoplastic drugs using in silico predictions.ResultsAs a result of analyzing the relationship between the effects of food and physicochemical properties, we found that compounds that show increased absorption in the fed state had higher logP and lower solubility in fasted-state simulated intestinal fluid (FaSSIF). However, compounds with delayed absorption had higher solubility in FaSSIF. Furthermore, as a result of decision tree analysis, it was classified as AUC increase with logP ≥4.34. We found that an AUC increase in the fed state did not occur with compounds with low lipid solubilities (logP < 1.59). From these results, it is predicted that 7 compounds out of the 24 compounds for which the effects of food are unknown are at risk for increased absorption in the fed state and that no increase in absorption would occur in 13 compounds.ConclusionIn this study, we found that drugs that will show increased absorption in the fed state and drugs for which absorption is not dependent on food can generally be predicted by logP. These results suggest that logP can be a useful parameter for predicting the effects of food on drug absorption.
Highlights
Food is known to affect drug absorption by delaying gastric emptying time, altering gastrointestinal pH, stimulating bile flow, increasing splanchnic blood flow, or physically interacting with drugs
We review the pharmacokinetic changes caused by food in oral antineoplastic drugs and evaluate their relevance to the physicochemical properties of antineoplastic drugs by in silico predictions
Investigation of oral antineoplastic drugs We surveyed the literature on three kinds of pharmacokinetic changes, including the area under the curve of the drug concentration-time profile (AUC) ratio, the maximum serum concentration (Cmax) ratio, and the time at which Maximum serum concentration (Cmax) is observed (Tmax) ratio, in the fasted and fed state for 72 oral antineoplastic drugs that were listed on the drug price standard in May 2018 in Japan [15]
Summary
Food is known to affect drug absorption by delaying gastric emptying time, altering gastrointestinal pH, stimulating bile flow, increasing splanchnic blood flow, or physically interacting with drugs. The Biopharmaceutics Classification System (BCS) is a scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability [5]. According to the BCS, drug substances are classified as four categories based on their solubility and intestinal permeability. Fisher et al reported that drug-food interactions could generally be Omachi et al Journal of Pharmaceutical Health Care and Sciences (2019) 5:26 predicted based on the BCS class [6]. Gu CH et al further improved the prediction of food effects by classifying drugs based on solubility, permeability and dose of a compound [8]. They analyzed 90 marketed compounds, only one oral antineoplastic drug was included in their models
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