Department of Pharmaceutical Sciences, School of Pharmacy, Husson University, One College Circle, Bangor, ME, USA.
Office of Clinical Pharmacology, U.S. Food and Drug Administration (FDA), Silver Springs, MD, USA.
AAPS J. 2021 Mar 21;23(3):47. doi: 10.1208/s12248-021-00570-4.
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 f > 10% is unlikely to be affected by food, although the peak plasma concentration (C) may increase or decrease by up to 50%. Compared with IR drug products with f > 10%, MR drug products with f > 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.
进食可通过改变药物的吸收、代谢和排泄来影响口服药物的药代动力学。主要以母体药物形式经尿液排泄的药物通常具有较高的水溶性和代谢稳定性。因此，预计进食不会显著影响其口服吸收、代谢和排泄程度。因此，我们假设具有显著肾排泄的口服药物不应具有明显的食物效应（FE）。为了验证我们的假设，我们总结了 1998 年至 2019 年美国 FDA 批准的口服速释（IR）和缓释（MR）制剂的 FE，重点关注具有显著肾排泄的药物。总共选择了 98 种 IR 制剂中的活性药物成分（API）和 34 种 MR 制剂中的 API。结果表明，f>10%的 IR 药物产品的曲线下面积（AUC）不太可能受到食物的影响，尽管峰血浆浓度（C）可能增加或减少高达 50%。与 f>10%的 IR 药物产品相比，f>10%的 MR 药物产品往往具有更显著的 FE。虽然我们提出的方法不能替代临床 FE 研究，但它可以作为早期药物开发的有用补充，以初步了解候选药物的 FE 潜力。
