Critical considerations for co-administering rivaroxaban and vonoprazan: Unveiling potential pharmacokinetic interactions.

Xiao-Yu Xu, Zhe-Yan Zhang, Xiao-Dan Zhang, Jian-Chao Luo, Yun-Shan Zhong, Le-Hao Jin, Da-Peng Dai, Jian-Chang Qian
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Abstract

To study the effects of metabolic enzyme activity inhibition and genetic polymorphisms on the pharmacokinetics and pharmacodynamics of rivaroxaban, we established an in vitro enzymatic reaction system to screen for inhibitors, and used the UPLC-MS/MS method to detect the levels of rivaroxaban and its metabolite M2-1. Additionally, in vivo pharmacokinetic-pharmacodynamic studies were conducted using Sprague-Dawley rats. Human recombinant CYP2J2 baculosomes were prepared using a baculovirus-insect expression system to investigate the impact of genetic polymorphisms on rivaroxaban metabolism through enzyme kinetics methods. The results demonstrated that acid-suppressing drugs strongly inhibited the metabolism of rivaroxaban in vitro. Among them, vonoprazan significantly increased the systemic exposure of rivaroxaban in vivo, while also prolonging prothrombin time, likely due to the competitive binding of vonoprazan and rivaroxaban to CYP2J2. Moreover, the genetic polymorphisms of CYP2J2 determined the metabolic characteristics of rivaroxaban and the inhibitory potency of vonoprazan. Overall, our findings suggest that vonoprazan-induced inhibition of CYP2J2 activity can affect the pharmacokinetics and pharmacodynamics of rivaroxaban, with the extent of inhibition determined by the genetic polymorphism of CYP2J2. These insights have important implications for the precise management of rivaroxaban in humans.

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麦克林 Rivaroxaban
麦克林 Ammonium acetate
麦克林 Rivaroxaban
麦克林 Ammonium Acetate
阿拉丁 Omeprazole sodium
阿拉丁 Esomeprazole Sodium
阿拉丁 Esomeprazole sodium
阿拉丁 Omeprazole Sodium
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