Effects of Vitamin D Receptor, Cytochrome P450 3A, and Cytochrome P450 Oxidoreductase Genetic Polymorphisms on the Pharmacokinetics of Remimazolam in Healthy Chinese Volunteers.
Adult
Asian People
/ genetics
Benzodiazepines
/ blood
Cytochrome P-450 CYP3A
/ genetics
Cytochrome P-450 Enzyme System
/ genetics
Female
Genotype
Healthy Volunteers
Humans
Hypnotics and Sedatives
/ blood
Injections, Intravenous
Male
Midazolam
/ pharmacokinetics
Polymorphism, Single Nucleotide
Receptors, Calcitriol
/ genetics
Young Adult
drug metabolism
genetic polymorphisms
pharmacokinetics
remimazolam
vitamin D receptor
Journal
Clinical pharmacology in drug development
ISSN: 2160-7648
Titre abrégé: Clin Pharmacol Drug Dev
Pays: United States
ID NLM: 101572899
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
15
12
2019
accepted:
21
02
2020
pubmed:
7
4
2020
medline:
16
12
2021
entrez:
7
4
2020
Statut:
ppublish
Résumé
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
Substances chimiques
Hypnotics and Sedatives
0
POR protein, human
0
Receptors, Calcitriol
0
VDR protein, human
0
Benzodiazepines
12794-10-4
remimazolam
7V4A8U16MB
Cytochrome P-450 Enzyme System
9035-51-2
CYP3A protein, human
EC 1.14.14.1
Cytochrome P-450 CYP3A
EC 1.14.14.1
Midazolam
R60L0SM5BC
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
22-29Informations de copyright
© 2020, The American College of Clinical Pharmacology.
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