雷米佐胺的药物-药物相互作用潜力：CYP450、转运体和蛋白结合。
Drug-Drug Interaction Potential of Remimazolam: CYP 450, Transporters, and Protein Binding.
机构信息
Department Pharmacology, RWTH Aachen University, Aachen, Germany.
Schmalix PharmaConsult, Gröbenzell, Germany.
出版信息
Curr Drug Metab. 2024;25(4):266-275. doi: 10.2174/0113892002300657240521094732.
BACKGROUND
The ultra-short-acting benzodiazepine, remimazolam, is a new treatment modality for procedural sedation and general anesthesia. Its activity is terminated by carboxylesterase 1 (CES1).
OBJECTIVE
The objective of this study was to determine the drug-drug interaction (DDI) potential of remimazolam through mechanisms unrelated to its metabolizing enzyme, CES1.
METHODS
Conventional in vitro co-exposure experiments were conducted to study possible interactions of remimazolam and its primary metabolite, CNS7054, mediated by competitive binding to plasma protein or reactions with cytochrome P450 isoforms or drug transporters.
RESULTS
No relevant interactions of remimazolam or its metabolite with cytochrome P450 (CYP) isoforms at clinically relevant concentrations were identified. Likewise, standard experiments revealed no clinically relevant interactions with drug transporters and plasma proteins.
CONCLUSION
The present data and analyses suggest a very low potential of remimazolam for pharmacokinetic DDIs mediated by CYP isoforms, drug transporters, and protein binding.
背景
超短效苯二氮䓬类药物瑞马唑仑是一种新的治疗程序镇静和全身麻醉的方法。其活性由羧酸酯酶 1（CES1）终止。
目的
本研究旨在通过与代谢酶 CES1 无关的机制来确定瑞马唑仑的药物相互作用（DDI）潜力。
方法
进行常规的体外共同暴露实验，以研究瑞马唑仑及其主要代谢物 CNS7054 通过与血浆蛋白的竞争性结合或与细胞色素 P450 同工酶或药物转运体的反应介导的可能相互作用。
结果
未在临床相关浓度下鉴定出瑞马唑仑或其代谢物与细胞色素 P450（CYP）同工酶的相关相互作用。同样，标准实验未发现与药物转运体和血浆蛋白有临床相关的相互作用。
结论
目前的数据和分析表明，瑞马唑仑通过 CYP 同工酶、药物转运体和蛋白结合介导的药代动力学 DDI 的潜力非常低。
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