Department of Pharmacy, Peking University First Hospital, Beijing, China.
Yichang Humanwell Pharmaceutical CO., LTD., Hubei, China.
Clin Pharmacol Drug Dev. 2021 Jan;10(1):22-29. doi: 10.1002/cpdd.797. Epub 2020 Apr 6.
Remimazolam is a new ultra-short-acting benzodiazepine used to induce and maintain anesthesia and procedural sedation. Its compound structure is similar to midazolam's. Midazolam metabolism might be affected by vitamin D receptor (VDR), cytochrome P450 3A, and cytochrome P450 oxidoreductase genetic polymorphisms. This study investigated the effects of VDR, cytochrome P450 3A, and cytochrome P450 oxidoreductase genetic polymorphisms on the pharmacokinetics of remimazolam in healthy Chinese volunteers after a single intravenous injection of remimazolam besylate. Blood samples were collected from subjects (n = 62) at scheduled time intervals before and after injection. High-performance liquid chromatography-tandem mass spectrometry was used to quantify plasma remimazolam and RF7054 (its inactive carboxylic acid metabolite) concentrations. The relationship between plasma remimazolam concentration, pharmacokinetic parameters, and polymorphic alleles was assessed for each subject. The rs4516035 allele affected the elimination half-life of RF7054 (P = .043), while the rs1544410 allele affected the dose-normalized maximum observed plasma concentration (C /D) of remimazolam (P = .025) in 46 volunteers. Results showed that VDR genetic polymorphisms might affect the pharmacokinetics of remimazolam in the Chinese population.
雷米唑仑是一种新型超短效苯二氮䓬类药物，用于诱导和维持全身麻醉及操作镇静。其化合物结构与咪达唑仑相似。维生素 D 受体（VDR）、细胞色素 P4503A 和细胞色素 P450 氧化还原酶的遗传多态性可能会影响咪达唑仑的代谢。本研究考察了 VDR、细胞色素 P4503A 和细胞色素 P450 氧化还原酶遗传多态性对健康中国志愿者单次静脉注射雷米唑仑苯磺酸盐后雷米唑仑药代动力学的影响。在注射前后的预定时间间隔内从受试者（n = 62）采集血样。采用高效液相色谱-串联质谱法测定血浆雷米唑仑和 RF7054（其无活性羧酸代谢物）的浓度。评估了每个受试者的血浆雷米唑仑浓度、药代动力学参数和多态性等位基因之间的关系。rs4516035 等位基因影响 RF7054 的消除半衰期（P =.043），而 rs1544410 等位基因影响 46 名志愿者中雷米唑仑的剂量标准化最大观察血浆浓度（C / D）（P =.025）。结果表明，VDR 遗传多态性可能会影响中国人群中雷米唑仑的药代动力学。
