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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
Abstract
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.
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“Remimazolam is hydroxylated by plasma tissue esterase to the inactive metabolite CNS 7054, which does not rely on kidney and liver metabolism (24,25).”
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“Long-term infusions or administering massive doses do not result in the accumulation of the drug or its metabolite, making it superior to midazolam and propofol.”
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“Similar to midazolam, remimazolam enhances γ-aminobutyric acid A (GABAA) receptor activity to induce cell membrane hyperpolarization, thereby inhibiting neural activity via an increase in chloride influx [3].”
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“Hu et al. conducted an observational study in 62 healthy Chinese volunteers investigating how remimazolam pharmacokinetics are influenced by genetic variations in the vitamin D receptor ( VDR ), cytochrome P450 3A ( CYP3A ), and cytochrome P450 Oxidoreductase ( POR ) genes [77].”
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“Hu et al. demonstrated that genetic factors affect the metabolism of midazolam and similar effects could be seen with remimazolam as well [22].”
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“Remimazolam, a novel ultra-short-acting benzodiazepine, metabolism is rapid, making it theoretically a safer option when prolonged sedation is necessary 8–10 , particularly in patients with compromised hepatic or renal function 11,12 .”
Illias, A. M., Tsai, Y.-F., & Wu, S.-C. (2026) · Drug Design, Development and Therapy · doi:10.2147/dddt.s644446
Jiang, P.-P., Deng, M., Wang, Q., Feng, Y., Wang, D., & Chen, X.-M. (2026) · Drug Design, Development and Therapy · doi:10.2147/dddt.s645319
Fu, K., Wang, Y., Duan, L., Zhang, Z., Qian, J., Chen, X.-J., Liang, Y., Lu, C., & Zhao, D. (2025) · Pharmaceuticals · doi:10.3390/ph18111615
“Previous studies have indicated that CYP3A genetic polymorphisms rarely produce clinically meaningful variability in ibrutinib pharmacokinetics, which aligns with our findings showing minimal effects of CYP3A4/5 variants in this cohort [24].”
Self-citationResearch Progress of Remimazolam in Induction and Maintenance of General An-esthesia
Yan, J.-W. (2022) · Advances in Clinical Medicine · doi:10.12677/acm.2022.126759
Metadata
- Authors
- Hu, K., Xiang, Q., Wang, Z., Sheng, X., Li, L., Liang, Y., Zhao, X., Ye, X., & Cui, Y.
- Affiliations
- Peking University First Hospital (CN)
- Yichang Humanwell Pharmaceutical CO., LTD. Hubei China
- Corresponding author
- Cui, Yimin
- Venue
- Clinical Pharmacology in Drug Development
- Publisher
- Wiley
- Published
- 2020-04-06
- Volume
- 10
- Issue
- 1
- Pages
- 22-29
- ISSN
- 2160-763X (ISSN-L)
- 2160-7648
- OpenAlex
- W3014720336
- Cited by
- 17
- References
- 0
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 4
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Pharmacology in Drug Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81872940, 81973395)
- Natural Science Foundation of Beijing Municipality (7171012)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- remimazolam, vitamin D receptor, CYP3A, genetic polymorphism, pharmacokinetics, benzodiazepines, midazolam metabolism, elimination half-life, Chinese population
- MeSH terms
- Adult, Benzodiazepines, Cytochrome P-450 Enzyme System, Female, Genotype, Humans, Hypnotics and Sedatives, Injections, Intravenous, Male, Midazolam, Receptors, Calcitriol, Polymorphism, Single Nucleotide, Asian People, Cytochrome P-450 CYP3A, Young Adult, Healthy Volunteers
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