Assessing Food Effects on Oral Drug Absorption Based on the Degree of Renal Excretion.

Food intake influences the pharmacokinetics of orally administered drugs by altering drug absorption, metabolism, and excretion. A drug which is mainly excreted into urine as parent drug is usually highly water-soluble and metabolically stable. Food intake is not expected to significantly affect its extent of oral absorption, metabolism, and excretion. Therefore, we hypothesize that an orally administered drug with significant renal excretion should not have a dramatic food effect (FE). To test our hypothesis, we summarized the FE for orally administered immediate-release (IR) and modified-release (MR) formulations approved by the US FDA from 1998 to 2019, focusing on drugs undergoing significant renal excretion. Totally, 98 active pharmaceutical ingredients (APIs) in IR formulations and 34 APIs in MR formulations were selected. The results demonstrate that the area-under-the-curve (AUC) for IR drug products with fur_unchanged_po > 10% is unlikely to be affected by food, although the peak plasma concentration (Cmax) may increase or decrease by up to 50%. Compared with IR drug products with fur_unchanged_po > 10%, MR drug products with fur_unchanged_po > 10% tend to have more significant FE. Although our proposed approach cannot substitute a clinical FE study, it could be a useful addition to early drug development to get an initial sense of the potential for FE for a drug candidate.