Drug, Meal and Formulation Interactions Influencing Drug Absorption After Oral Administration

Abstract

Drug-drug, drug-formulation and drug-meal interactions are of clinical concern for orally administered drugs that possess a narrow therapeutic index. This review presents the current status of information regarding interactions which may influence the gastrointestinal (GI) absorption of orally administered drugs. Absorption interactions have been classified on the basis of rate-limiting processes. These processes are put in the context of drug and formulation physicochemical properties and oral input influences on variable GI physiology. Interaction categorisation makes use of a biopharmaceutical classification system based on drug aqueous solubility and membrane permeability and their contributions towards absorption variability. Overlaying this classification it is important to be aware of the effect that the magnitudes of drug dosage and volume of fluid administration can have on interactions involving a solubility rate limits. GI regional differences in membrane permeability are fundamental to the rational 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. Although the clinical significance of such interactions is certainly dependent on the narrowness of the drug therapeutic index, clinical aspects of absorption delays and therapeutic failures resulting from various interactions are also important.

Formulation of enrofloxacin SLNs and its pharmacokinetics in emu (Dromaius novaehollandiae) birds

“…The increased absorption of enrofloxacin-loaded SLNs might have been contributed via six possible mechanisms. First, the SLNs formulations entering into the GI tract stimulated secretions of bile salts (BS), phospholipids (PL) and cholesterol, due to the presence of lipids in the formulation (Fleisher et al 1999;Dahan and Hoffman 2008). The SLNs products along with the gastric shear movement formed a crude emulsion.…”

Drug release from matrix tablets: physiological parameters and the effect of food

“…The differences in bioavailability when drug is administered in fed state versus the fasted state could be partly attributed to this compositional difference of the fed and fasted intestinal fluids [4]. This is as a result of interactions which may occur between the oral formulation of the drug and the food administered [86][87][88][89][90].…”

Challenges and Opportunities in Achieving Bioequivalence for Fixed-Dose Combination Products

“…In addition, the interplay of physicochemical properties of drugs and food can result in complex profiles in oral absorption and bioavailability. Fleisher et al summarized the general trend of food effect on drug absorption based on biopharmaceutical classification system (BCS) (41). BCS class I compounds are likely to have no food effect on exposure, primarily because absorption of highly soluble and highly permeable drugs is usually pH-and site-independent and thus insensitive to differences in dissolution; BCS class II compounds are likely to have positive food effect (increased absorption); BCS class III compounds are likely to have negative food effect (decreased absorption), and there is no clear trend for BCS class IV compounds.…”