Influence of Food Intake on Drug Absorption and Systemic Bioavailability

How an orally dosed small-molecule drug is absorbed depends heavily on its chemical makeup and the body's digestive environment. A key challenge is the difference between fed and fasted states: eating alters gut transit times and complicates oral absorption estimates, making food-effect studies necessary across every Biopharmaceutics Classification System (BCS) category. Food intake sets off major gastrointestinal changes—shifting stomach and bowel pH, slowing gastric emptying, boosting bile release, and increasing blood flow to the liver and gut.Although these physiological shifts directly dictate how well a drug dissolves and enters circulation, dietary influences are still routinely overlooked and under-researched. Physiologically based pharmacokinetic (PBPK) simulations bridge this gap by modeling drug disposition under fed and fasted conditions alongside intrinsic properties like permeability and solubility.This paper surveys existing literature on PBPK models built to capture food effects, weighing their core capabilities, current flaws, and areas for refinement. Today's models struggle most with anticipating reduced absorption (negative food effects) and mapping outcomes in children. Improving these computational tools will yield a clearer mechanistic understanding of feeding-related drug variations and significantly improve oral formulation development.