Identification of genetic biomarkers associated with pharmacokinetics and pharmacodynamics of apixaban in Chinese healthy volunteers
BACKGROUND: Apixaban is a superior direct oral anticoagulant exihibiting interindividual variability in concentration and response in the real world. The present study aimed to identify genetic biomarkers associated with pharmacokinetics (PK) and pharmacodynamics (PD) of apixaban in healthy Chinese subjects.
METHODS: This multicenter study included 181 healthy Chinese adults taking a single dose of 2.5 mg or 5 mg apixaban and assessed their PK and PD parameters. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed using the Affymetrix Axiom CBC_PMRA Array. Candidate gene association analysis and genome-wide association study were conducted to identify genes with a predictive value for PK and PD parameters of apixaban.
RESULTS: Several ABCG2 variants were associated with Cmax and AUC0-t of apixaban (p < 6.12 × 10-5) and also presented significant differences of anti-Xa3h activity and dPT3h according to different ABCG2 genotypes (p < 0.05). Besides, ABLIM2 variants were found to be associated with PK characteristics and F13A1 and C3 variants were associated with PD characteristics of apixaban (p < 9.46 × 10-8).
CONCLUSION: ABCG2 variants were found to be ideal genetic biomarkers for both PK and PD characteristics of apixaban. ABLIM2, F13A1 and C3 were identified as potential candidate genes associated with inter-individual variability of apixaban. This study was registered on ClinicalTrials.gov NCT03259399.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
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| Enthalten in: |
Expert opinion on drug metabolism & toxicology - 19(2023), 1 vom: 01. Jan., Seite 43-51 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mu, Guangyan [VerfasserIn] |
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| Links: |
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| Themen: |
3Z9Y7UWC1J |
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| Anmerkungen: |
Date Completed 31.03.2023 Date Revised 31.03.2023 published: Print-Electronic ClinicalTrials.gov: NCT03259399 Citation Status MEDLINE |
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| doi: |
10.1080/17425255.2023.2184344 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM353734020 |
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| 245 | 1 | 0 | |a Identification of genetic biomarkers associated with pharmacokinetics and pharmacodynamics of apixaban in Chinese healthy volunteers |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 31.03.2023 | ||
| 500 | |a Date Revised 31.03.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03259399 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Apixaban is a superior direct oral anticoagulant exihibiting interindividual variability in concentration and response in the real world. The present study aimed to identify genetic biomarkers associated with pharmacokinetics (PK) and pharmacodynamics (PD) of apixaban in healthy Chinese subjects | ||
| 520 | |a METHODS: This multicenter study included 181 healthy Chinese adults taking a single dose of 2.5 mg or 5 mg apixaban and assessed their PK and PD parameters. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed using the Affymetrix Axiom CBC_PMRA Array. Candidate gene association analysis and genome-wide association study were conducted to identify genes with a predictive value for PK and PD parameters of apixaban | ||
| 520 | |a RESULTS: Several ABCG2 variants were associated with Cmax and AUC0-t of apixaban (p < 6.12 × 10-5) and also presented significant differences of anti-Xa3h activity and dPT3h according to different ABCG2 genotypes (p < 0.05). Besides, ABLIM2 variants were found to be associated with PK characteristics and F13A1 and C3 variants were associated with PD characteristics of apixaban (p < 9.46 × 10-8) | ||
| 520 | |a CONCLUSION: ABCG2 variants were found to be ideal genetic biomarkers for both PK and PD characteristics of apixaban. ABLIM2, F13A1 and C3 were identified as potential candidate genes associated with inter-individual variability of apixaban. This study was registered on ClinicalTrials.gov NCT03259399 | ||
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Apixaban | |
| 650 | 4 | |a candidate gene | |
| 650 | 4 | |a genome-wide association analysis | |
| 650 | 4 | |a pharmacodynamics | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 7 | |a apixaban |2 NLM | |
| 650 | 7 | |a 3Z9Y7UWC1J |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Factor Xa Inhibitors |2 NLM | |
| 700 | 1 | |a Xie, Qiufen |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhiyan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hanxu |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Xianmin |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Jinfang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Shuang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zining |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Maoxing |e verfasserin |4 aut | |
| 700 | 1 | |a Bao, Jiachun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Xiang, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Yimin |e verfasserin |4 aut | |
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