Interactions affecting drug absorption.

The influence of drug-drug and drug-food interactions affecting the absorption of orally administered medication is reviewed. Drug-drug interactions can be classified in terms of indirect effects by one drug on gastrointestinal tract physiology influencing the absorption of other drugs, or direct interactions involving altered pH, adsorption, absorption, or chelation. Most, but not all, drug-drug interactions result in reduced or delayed systemic drug availability. Drug-food interactions may result in reduced, delayed, or increased systemic drug availability. The absorption of only a small number of drugs is unaffected by concomitant food intake. The degree of interaction and whether it positively or negatively affects drug absorption depends on a number of factors including the physical and chemical nature of the drug, the formulation, the type of meal, and the time interval between eating and dosing. Mechanisms of drug-food interactions are not well characterised. They clearly involve both direct and indirect factors in a similar fashion to drug-drug interactions, but indirect factors probably predominate. Reduced or delayed drug absorption is generally attributed, at least in part, to delayed stomach-emptying due to food. Increased absorption may also result from delayed stomach-emptying facilitating greater drug dissolution before it passes from the stomach into the small intestine. Increased bioavailability of some drugs, e.g. propranolol, metoprolol and labetalol, may be related to reduced presystemic clearance. The potential clinical implications of drug-drug and drug-food interactions must be taken into account with oral medications in order to minimise variations in systemic drug availability and hence in clinical efficacy.