Liu Jiaqi, Hahn Jongsung
Department of Pharmacy, Jeonbuk National University, Jeonju, Jeollabuk, Republic of Korea.
Front Pharmacol. 2025 Jul 8;16:1580969. doi: 10.3389/fphar.2025.1580969. eCollection 2025.
Potassium competitive acid blockers (P-CABs) are a new class of acid suppressants that provide rapid and sustained inhibition of gastric acid secretion. Understanding the pharmacokinetic (PK) characteristics of P-CABs in various therapeutic uses is essential for optimizing treatment. This study aims to investigate the PK properties of P-CABs, focusing on drug interactions, food effects, and formulation impacts on their exposure and bioavailability.
We systematically searched MEDLINE and Embase up to July 2024. The search terms included "Potassium competitive acid blockers" or "P-CABs" or "revaprazan" or "vonoprazan" or "tegoprazan" or "fexuprazan" or "keverprazan" or "zastaprazan" and "pharmacokinetics".
A total of 37 studies were included. Meta-analysis and qualitative studies indicated that clarithromycin significantly increased vonoprazan and tegoprazan exposure [geometric mean ratio (GMR) (90% confidence interval (CI))] of AUC and Cmax: 1.565 (1.443, 1.687) and 1.538 (1.454, 1.621) for vonoprazan, 2.624 (2.513, 2.735) and 1.876 (1.771, 1.981) for tegoprazan, respectively. Vonoprazan had more of an inhibitory effect on cytochrome P450 (CYP) 3A and CYP2C19 compared to tegoprazan. P-CABs showed minimal interactions with nonsteroidal anti-inflammatory drugs or aspirin and were largely unaffected by food intake, except keverprazan and zastaprazan, which showed increased exposure.
It is important to select the appropriate P-CABs by considering the degree of influence on CYP enzymes, the dosage form, and food interactions. Studies on the interaction between P-CABs and antibiotics used to treat infections, such as metronidazole, tetracycline, levofloxacin, or rifabutin, as well as non-vitamin K antagonist oral anticoagulants are lacking, and further research is needed.
钾离子竞争性酸阻滞剂（P-CABs）是一类新型的抑酸剂，可快速且持续地抑制胃酸分泌。了解P-CABs在各种治疗用途中的药代动力学（PK）特征对于优化治疗至关重要。本研究旨在调查P-CABs的PK特性，重点关注药物相互作用、食物影响以及制剂对其暴露和生物利用度的影响。
我们系统检索了截至2024年7月的MEDLINE和Embase。检索词包括“钾离子竞争性酸阻滞剂”或“P-CABs”或“瑞伐拉唑”或“沃克奥美拉唑”或“替戈拉赞”或“非索拉唑”或“凯韦拉唑”或“扎斯塔拉唑”以及“药代动力学”。
共纳入37项研究。荟萃分析和定性研究表明，克拉霉素显著增加了沃克奥美拉唑和替戈拉赞的暴露量[曲线下面积（AUC）和血药浓度峰值（Cmax）的几何平均比值（GMR）（90%置信区间（CI））]：沃克奥美拉唑的AUC和Cmax的GMR分别为1.565（1.443，1.687）和1.538（1.454，1.621），替戈拉赞的分别为2.624（2.513，2.735）和1.876（1.771，1.981）。与替戈拉赞相比，沃克奥美拉唑对细胞色素P450（CYP）3A和CYP2C19的抑制作用更强。P-CABs与非甾体抗炎药或阿司匹林的相互作用最小，并且在很大程度上不受食物摄入的影响，但凯韦拉唑和扎斯塔拉唑除外，它们的暴露量增加。
通过考虑对CYP酶的影响程度、剂型和食物相互作用来选择合适的P-CABs很重要。目前缺乏关于P-CABs与用于治疗感染的抗生素（如甲硝唑、四环素、左氧氟沙星或利福布汀）以及非维生素K拮抗剂口服抗凝剂之间相互作用的研究，需要进一步开展研究。
