The Pharmacogenetic Variability Associated With the Pharmacokinetics and Pharmacodynamics of Rivaroxaban in Healthy Chinese Subjects : A National Multicenter Exploratory Study
Copyright © 2024 Elsevier Inc. All rights reserved..
PURPOSE: This study aimed to explore the pharmacogenetic variability associated with the pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in healthy Chinese subjects.
METHODS: This was a multicenter study that included 304 healthy adults aged 18 to 45 years with unknown genotypes. All participants were administered a single dose of rivaroxaban at 10 mg, 15 mg, or 20 mg. PK and PD parameters were measured, and exome-wide association analysis was conducted.
FINDINGS: Sixteen SNPs located on 11 genes influenced the AUC0-t. Among these, the 3 most influential genes were MiR516A2, PARP14, and MIR618. Thirty-six SNPs from 28 genes were associated with the PD of rivaroxaban. The 3 most influential genes were PKNOX2, BRD3, and APOL4 for anti-Xa activity, and GRIP2, PLCE1, and MLX for diluted prothrombin time (dPT). Among them, BRD3 played an important role in both the PK and PD of rivaroxaban. Anti-Xa activity (ng/mL) differed significantly among subjects with BRD3 rs467387: 145.1 ± 55.5 versus 139.9 ± 65.1 versus 164.0 ± 68.6 for GG, GA, and AA carriers, respectively (P = 0.0002).
IMPLICATIONS: This study found that that the regulation of the BRD3 gene might affect the PK and PD of rivaroxaban, suggesting that it should be studied as a new pharmacologic target. The correlation between this gene locus and clinical outcomes has yet to be verified in patients undergoing clinical treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Clinical therapeutics - (2024) vom: 28. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Zhiyan [VerfasserIn] |
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| Links: |
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| Themen: |
Gene polymorphism |
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| Anmerkungen: |
Date Revised 29.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.clinthera.2024.02.009 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM37042851X |
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| 100 | 1 | |a Liu, Zhiyan |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The Pharmacogenetic Variability Associated With the Pharmacokinetics and Pharmacodynamics of Rivaroxaban in Healthy Chinese Subjects |b A National Multicenter Exploratory Study |
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| 520 | |a Copyright © 2024 Elsevier Inc. All rights reserved. | ||
| 520 | |a PURPOSE: This study aimed to explore the pharmacogenetic variability associated with the pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in healthy Chinese subjects | ||
| 520 | |a METHODS: This was a multicenter study that included 304 healthy adults aged 18 to 45 years with unknown genotypes. All participants were administered a single dose of rivaroxaban at 10 mg, 15 mg, or 20 mg. PK and PD parameters were measured, and exome-wide association analysis was conducted | ||
| 520 | |a FINDINGS: Sixteen SNPs located on 11 genes influenced the AUC0-t. Among these, the 3 most influential genes were MiR516A2, PARP14, and MIR618. Thirty-six SNPs from 28 genes were associated with the PD of rivaroxaban. The 3 most influential genes were PKNOX2, BRD3, and APOL4 for anti-Xa activity, and GRIP2, PLCE1, and MLX for diluted prothrombin time (dPT). Among them, BRD3 played an important role in both the PK and PD of rivaroxaban. Anti-Xa activity (ng/mL) differed significantly among subjects with BRD3 rs467387: 145.1 ± 55.5 versus 139.9 ± 65.1 versus 164.0 ± 68.6 for GG, GA, and AA carriers, respectively (P = 0.0002) | ||
| 520 | |a IMPLICATIONS: This study found that that the regulation of the BRD3 gene might affect the PK and PD of rivaroxaban, suggesting that it should be studied as a new pharmacologic target. The correlation between this gene locus and clinical outcomes has yet to be verified in patients undergoing clinical treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Gene polymorphism | |
| 650 | 4 | |a Pharmacodynamics | |
| 650 | 4 | |a Pharmacokinetics | |
| 650 | 4 | |a Rivaroxaban | |
| 700 | 1 | |a Xie, Qiufen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Yunlong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Wenping |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Xiaohua |e verfasserin |4 aut | |
| 700 | 1 | |a Mu, Guangyan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hanxu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Shuang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiaobin |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Song |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Duanwen |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Yimin |e verfasserin |4 aut | |
| 700 | 1 | |a Xiang, Qian |e verfasserin |4 aut | |
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