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
Authors: Hu, Kun; Xiang, Qian; Wang, Zhe; Sheng, Xiaoyan; Li, Li'e; Liang, Yan; Zhao, Xia; Ye, Xia; Cui, Yimin
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.
Effects of host genetic variations on response to, susceptibility and severity of respiratory infections
BIOMEDICINE & PHARMACOTHERAPY
Authors: Ghafouri-Fard, Soudeh; Noroozi, Rezvan; Vafaee, Reza; Branicki, Wojciech; Pospiech, Ewelina; Pyrc, Krzysztof; Labaj, Pawel P.; Omrani, Mir Davood; Taheri, Mohammad; Sanak, Marek
Abstract
The recent outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a global crisis, necessitating the identification of genetic factors that modulate the risk of disorder or its severity. The current data about the role of genetic risk factors in determination of rate of SARS-CoV-2 infection in each ethnic group and the severity of disorder is limited. Moreover, several confounding parameters such as the number of tests performed in each country, the structure of the population especially the age distribution, the presence of risk factors for respiratory disorders such as smoking and other environmental factors might be involved in the variability in disease course or prevalence of infection among different ethnic groups. However, assessment of the role of genetic variants in determination of the course of other respiratory infections might help in recognition of possible candidate for further analysis in patients affected with SARS-CoV-2. In the current review, we summarize the data showing the association between genomic variants and risk of acute respiratory distress syndrome, respiratory infections or severity of these conditions with an especial focus on the SARS-CoV-2.