Drug, meal and formulation interactions influencing drug absorption after oral administration - Clinical implications

Drug-drug, drug-formulation and drug-meal interactions are of clinical conc ern for orally administered drugs that possess a narrow therapeutic index. This review presents the current status of information regarding interactio ns which may influence the gastrointestinal (GI) absorption of orally admin istered drugs. Absorption interactions have been classified on the basis of rate-limiting processes. These processes are put in the context of drug and formulation p hysicochemical properties and oral input influences on variable GI physiolo gy. Interaction categorisation makes use of a biopharmaceutical classificat ion system based on drug aqueous solubility and membrane permeability and t heir contributions towards absorption variability. Overlaying this classifi cation it is important to be aware of the effect that the magnitudes of dru g dosage and volume of fluid administration can have on interactions involv ing a solubility rate limits. GI regional differences in membrane permeability are fundamental to the rat ional development of extended release dosage forms as well as to predicting interaction effects on absorption from immediate release dosage forms. The effect of meals on the regional-dependent intestinal elimination of drugs and their involvement in drug absorption interactions is also discussed. Al though the clinical significance of such interactions is certainly dependen t on the narrowness of the drug therapeutic index, clinical aspects of abso rption delays and therapeutic failures resulting from various interactions are also important.