Predicting drug disposition, absorption/elimination/transporter interplay and the role of food on drug absorption

Advanced Drug Delivery Reviews
Joseph M CustodioLeslie Z Benet

Abstract

The ability to predict drug disposition involves concurrent consideration of many chemical and physiological variables and the effect of food on the rate and extent of availability adds further complexity due to postprandial changes in the gastrointestinal (GI) tract. A system that allows for the assessment of the multivariate interplay occurring following administration of an oral dose, in the presence or absence of meal, would greatly benefit the early stages of drug development. This is particularly true in an era when the majority of new molecular entities are highly permeable, poorly soluble, extensively metabolized compounds (BDDCS Class 2), which present the most complicated relationship in defining the impact of transporters due to the marked effects of transporter-enzyme interplay. This review evaluates the GI luminal environment by taking into account the absorption/transport/elimination interplay and evaluates the physiochemical property issues by taking into account the importance of solubility, permeability and metabolism. We concentrate on the BDDCS and its utility in predicting drug disposition. Furthermore, we focus on the effect of food on the extent of drug availability (F), which appears to follow closely wha...Continue Reading

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