Department of Pharmaceutics, University of Washington, H-272 Health Sciences Building, Box 357610, Seattle, Washington, 98195, USA.
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
AAPS J. 2021 Dec 27;24(1):16. doi: 10.1208/s12248-021-00667-w.
Food effect (FE) and gastric pH-dependent drug-drug interactions (DDIs) are both absorption-related. Here, we evaluated if Biopharmaceutics Classification System (BCS) classes may be correlated with FE or pH-dependent DDIs. Trends in FE data were investigated for 170 drugs with clinical FE studies from the literature and new drugs approved from 2013 to 2019 by US Food and Drug Administration. A subset of 38 drugs was also evaluated to determine whether FE results can inform the need for a gastric pH-dependent DDI study. The results of FE studies were defined as no effect (AUC ratio 0.80-1.25), increased exposure (AUC ratio ≥1.25), or decreased exposure (AUC ratio ≤0.8). Drugs with significantly increased exposure FE (AUC ratio ≥2.0; N=14) were BCS Class 2 or 4, while drugs with significantly decreased exposure FE (AUC ratio ≤0.5; N=2) were BCS Class 1/3 or 3. The lack of FE was aligned with the lack of a pH-dependent DDI for all 7 BCS Class 1 or 3 drugs as expected. For the 13 BCS Class 2 or 4 weak base drugs with an increased exposure FE, 6 had a pH-dependent DDI (AUC ratio ≤0.8). Among the 16 BCS Class 2 or 4 weak base drugs with no FE, 6 had a pH-dependent DDI (AUC ratio ≤0.8). FE appears to have limited correlation with BCS classes except for BCS Class 1 drugs, confirming that multiple physiological mechanisms can impact FE. Lack of FE does not indicate absence of pH-dependent DDI for BCS Class 2 or 4 drugs. Graphical Abstract.
食物效应（FE）和胃 pH 依赖性药物相互作用（DDI）均与吸收相关。在此，我们评估了生物药剂学分类系统（BCS）类别是否与 FE 或 pH 依赖性 DDI 相关。通过评估文献中的 170 种具有临床 FE 研究的药物和美国食品药品监督管理局（FDA）2013 年至 2019 年批准的新药，研究了 FE 数据的趋势。还评估了 38 种药物的子集，以确定 FE 结果是否可以提供进行胃 pH 依赖性 DDI 研究的依据。FE 研究的结果定义为无影响（AUC 比值 0.80-1.25）、暴露增加（AUC 比值≥1.25）或暴露减少（AUC 比值≤0.8）。具有明显增加的 FE 暴露（AUC 比值≥2.0；N=14）的药物为 BCS 类别 2 或 4，而具有明显减少的 FE 暴露（AUC 比值≤0.5；N=2）的药物为 BCS 类别 1/3 或 3。如预期的那样，对于所有 7 种 BCS 类别 1 或 3 的无 FE 的药物，缺乏 FE 与缺乏 pH 依赖性 DDI 是一致的。在 13 种具有增加的 FE 暴露的 BCS 类别 2 或 4 弱碱性药物中，有 6 种具有 pH 依赖性 DDI（AUC 比值≤0.8）。在 16 种无 FE 的 BCS 类别 2 或 4 弱碱性药物中，有 6 种具有 pH 依赖性 DDI（AUC 比值≤0.8）。FE 与 BCS 类别之间似乎相关性有限，除了 BCS 类别 1 的药物，这证实了多种生理机制可能会影响 FE。对于 BCS 类别 2 或 4 的药物，缺乏 FE 并不表示不存在 pH 依赖性 DDI。
