The Effects of Food on Drug Bioavailability and Bioequivalence

Abstract

The effects of food on the drug absorption of orally dosed drug products are complex. These food effects can be specific, direct interactions between components of the food ingested and the drug substance or excipients themselves, or the food-effects can be secondary to the physiological changes in the gastrointestinal (GI) tract, which occur after ingesting the meal. These food-effects often have clinical significance. Food can change the bioavailability (BA) of a drug, which can in turn, alter its safety and/or efficacy profile. Likewise, food can influence the bioequivalence (BE) between a proposed generic drug product and its innovator counterpart (i.e., the reference listed drug product, or RLD). This chapter focuses on the complex effects of food on the absorption of drugs from the GI tract. In particular, it discusses the current US regulatory framework set forth by the Food and Drug Administration (FDA) in determining the impact of food on the absorption of orally dosed drug products. Case studies are discussed in order to show specific examples of the complex effects of food on drug absorption and BA, and how modified formulations might overcome at least some of these effects. After reading this chapter, the reader should have a general understanding of (1) how food can affect drug absorption from the GI tract, (2) why these food–drug interactions are relevant to the FDA and to US consumers, and (3) what types of BA and BE studies are recommended by the FDA for determining potential food-effects on drug absorption.