Evaluation of commonly used cardiovascular drugs in inhibiting vonoprazan metabolism in vitro and in vivo.
Evaluation of commonly used cardiovascular drugs in inhibiting vonoprazan metabolism in vitro and in vivo.
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DOI：
10.3389/fphar.2022.909168
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发表时间：
2022
影响因子：
5.6
通讯作者：
Luo, Qingfeng
中科院分区：
文献类型：
--
作者：
Wang, Yiran;Shi, Jihua;Dai, Dapeng;Cai, Jianping;Wang, Shuanghu;Hong, Yun;Zhou, Shan;Zhao, Fangling;Zhou, Quan;Geng, Peiwu;Zhou, Yunfang;Xu, Xue;Luo, Qingfeng
作为一种新型的抑酸药物，伏诺哌嗪显示出替代传统质子泵抑制剂的潜力。随着其广泛使用，由于药物与药物的相互作用，出现了一些需要进一步研究的不良反应。我们的研究是第一个评估11种常见心血管药物在体外和体内抑制伏诺哌嗪代谢的药物-药物相互作用的实验。采用大鼠肝微粒体孵育和分子模拟对接的方法探讨其抑制机制。在体外第一部分评价中，氨氯地平和硝苯地平对沃诺哌赞在大鼠和人肝微粒体中的代谢均有抑制作用。抑制机制分析结果表明，氨氯地平和硝苯地平可能以竞争性和非竞争性混合抑制方式抑制伏诺哌赞的代谢。然而，vonoprazan原型的药代动力学数据显示，氨氯地平在体内影响vonoprazan，而硝苯地平没有。因此，当氨氯地平与伏诺哌嗪合用时，应多加注意。此外，其羧酸代谢物MI的变化暗示了一个复杂的情况。分子模拟表明CYP2B6酶的作用可能比CYP3A4更大，进一步的抑制实验初步证实了这一推测。综上所述，临床处方中应特别注意vonoprazan与心血管药物，特别是氨氯地平的合用。
As a novel acid-suppressing drug, vonoprazan shows the potential to replace traditional proton-pump inhibitors. With its widespread use, some adverse effects that require further study have emerged due to drug–drug interactions. Our study is the first experiment that evaluated the drug–drug interactions of eleven common cardiovascular drugs that inhibit vonoprazan metabolism in vitro and in vivo. Rat liver microsome incubation and molecular simulation docking were applied to explore the inhibition mechanism. Amlodipine and nifedipine showed inhibitory effects on vonoprazan metabolism in both rat and human liver microsomes in the first evaluation part in vitro. The inhibition mechanism analysis results demonstrated that amlodipine and nifedipine might inhibit the metabolism of vonoprazan by a mixed type of competitive and non-competitive inhibition. However, the pharmacokinetic data of the vonoprazan prototype revealed that amlodipine affected vonoprazan in vivo while nifedipine did not. Thus, more attention should be paid when amlodipine is prescribed with vonoprazan. Furthermore, the changes in its carboxylic acid metabolites MI hinted at a complex situation. Molecular simulation suggested the CYP2B6 enzyme may contribute more to this than CYP3A4, and further inhibitory experiments preliminarily verified this speculation. In conclusion, the use of vonoprazan with cardiovascular drugs, especially amlodipine, should receive particular attention in clinical prescriptions.
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影响因子：
1.6
作者：
Kambara, H.;Hosohata, K.;Iwanaga, K.
通讯作者：
Iwanaga, K.
影响因子：
3.2
作者：
Kojima, Yuichi;Takeuchi, Toshihisa;Higuchi, Kazuhide
通讯作者：
Higuchi, Kazuhide
影响因子：
2
作者：
通讯作者：
--
DOI：
10.1073/pnas.1616198114
发表时间：
2017-01-17
影响因子：
11.1
作者：
Sevrioukova, Irina F.;Poulos, Thomas L.
通讯作者：
Poulos, Thomas L.
影响因子：
6.3
作者：
Kamada T;Satoh K;Itoh T;Ito M;Iwamoto J;Okimoto T;Kanno T;Sugimoto M;Chiba T;Nomura S;Mieda M;Hiraishi H;Yoshino J;Takagi A;Watanabe S;Koike K
通讯作者：
Koike K