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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).”
In the citing paper
“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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Remimazolam: non-clinical and clinical profile of a new sedative/anesthetic agent
Kilpatrick, G. J. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.690875 · Cited by 262
Zhang, X.-Q., Li, S., & Liu, J. (2021) · BMC Anesthesiology · doi:10.1186/s12871-021-01373-y · Cited by 146
“studies, remimazolam was effectively and safely used in Chinese volunteers [11, 25].”
BackgroundSedation outcomes for remimazolam, a new benzodiazepine.
Oka, S., Satomi, H., Sekino, R., Taguchi, K., Kajiwara, M., Oi, Y., & Kobayashi, R. (2021) · Journal of Oral Science · doi:10.2334/josnusd.21-0051 · Cited by 84
“Another important difference is that the hepatic drug-metabolizing enzyme CYP is not involved in metabolism and the metabolites are not active [12,13].”
BackgroundZhu, T. (2023) · Pain Physician Journal · doi:10.36076/ppj.2023.26.e761 · Cited by 42
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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- CoChat. (2026). Citation check: Effects of Vitamin D Receptor, Cytochrome P450 3A, and Cytochrome P450 Oxidoreductase Genetic Polymorphisms on the Pharmacokinetics of Remimazolam in Healthy Chinese Volunteers. https://app.cochat.ai/papers/10.1002/cpdd.797
- The paper
- Hu, K., Xiang, Q., Wang, Z., Sheng, X., Li, L., Liang, Y., Zhao, X., Ye, X., & Cui, Y. (2021). Effects of Vitamin D Receptor, Cytochrome P450 3A, and Cytochrome P450 Oxidoreductase Genetic Polymorphisms on the Pharmacokinetics of Remimazolam in Healthy Chinese Volunteers. Clinical Pharmacology in Drug Development. https://doi.org/10.1002/cpdd.797
