| Title | Evaluation of commonly used cardiovascular drugs in inhibiting vonoprazan metabolism in vitro and in vivo |
| Authors | 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 |
| Affiliation | Beijing Hosp, Chinese Acad Med Sci, Inst Geriatr Med, Natl Ctr Gerontol, Beijing, Peoples R China Peking Univ, Sch Clin Med 5, Beijing, Peoples R China Beijing Hosp, Beijing Inst Geriatr, Inst Geriatr Med, Chinese Acad Med Sci, Beijing, Peoples R China Wenzhou Med Univ, Hosp 6, Peoples Hosp Lishui, Lab Clin Pharm, Lishui, Peoples R China |
| Keywords | PROTON PUMP INHIBITORS COMPETITIVE ACID BLOCKER PHARMACOKINETICS SAFETY |
| Issue Date | 16-Aug-2022 |
| Publisher | FRONTIERS IN PHARMACOLOGY |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/652637 |
| DOI | 10.3389/fphar.2022.909168 |
| Indexed | SCI(E) |
| Appears in Collections: | 北京医院 |
