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Effects of Vitamin D Receptor, Cytochrome P450 3A, and Cytochrome P450 Oxidoreductase Genetic Polymorphisms on the Pharmacokinetics of Remimazolam in Healthy Chinese Volunteers
Author(s) -
Hu Kun,
Xiang Qian,
Wang Zhe,
Sheng Xiaoyan,
Li Li'e,
Liang Yan,
Zhao Xia,
Ye Xia,
Cui Yimin
Publication year - 2021
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.797
Subject(s) - pharmacokinetics , medicine , midazolam , pharmacology , cytochrome p450 , cyp3a4 , calcitriol receptor , cmax , cyp2c19 , cyp2b6 , metabolism , receptor , sedation
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 max /D) of remimazolam ( P = .025) in 46 volunteers. Results showed that VDR genetic polymorphisms might affect the pharmacokinetics of remimazolam in the Chinese population.