Correlation between the systemic clearance of drugs and their food effects in humans.

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.

Predictive models for drugs exhibiting negative food effects based on their biopharmaceutical characteristics.

Context: A drug is defined to exhibit food effects if its pharmacokinetic parameter, area under the curve (AUC₀₋∞) is different when co-administered with food in comparison with its administration on a fasted stomach. Food effects of drugs administered in immediate release dosage forms were classified as positive, negative, and no food effects.

Objective: In this study, predictive models for negative food effects of drugs that are stable in the gastrointestinal tract and do not complex with Ca²⁺ are reported.

Investigation of some factors contributing to negative food effects.

A drug is defined as exhibiting negative food effects, if the co-administration of food statistically decreases its area under the curve, AUC, when compared with its administration on a fasted stomach. In this study, the role of biopharmaceutical factors that contribute to negative food effects was studied using furosemide, nadolol, tacrine and atenolol (as model compounds exhibiting negative food effects), and prednisolone, hydrochlorothiazide and ibuprofen (as model compounds that do not show any food effects). The physiological pH of the upper intestinal tract is lower, at pH 5, in the postprandial state when compared with the preprandial state, pH 6.