{"title":"与阿哌沙班在中国健康志愿者体内药代动力学和药效学相关的遗传生物标志物的鉴定。","authors":"Guangyan Mu, Qiufen Xie, Zhiyan Liu, Hanxu Zhang, Xianmin Meng, Jinfang Song, Shuang Zhou, Zhe Wang, Zining Wang, Xia Zhao, Jie Jiang, Maoxing Liao, Jiachun Bao, Fan Zhang, Qian Xiang, Yimin Cui","doi":"10.1080/17425255.2023.2184344","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Several <i>ABCG2</i> variants were associated with C<sub>max</sub> and AUC<sub>0-t</sub> of apixaban (p < 6.12 × 10<sup>-5</sup>) and also presented significant differences of anti-Xa<sub>3h</sub> activity and dPT<sub>3h</sub> according to different <i>ABCG2</i> genotypes (p < 0.05). Besides, <i>ABLIM2</i> variants were found to be associated with PK characteristics and <i>F13A1</i> and C3 variants were associated with PD characteristics of apixaban (p < 9.46 × 10<sup>-8</sup>).</p><p><strong>Conclusion: </strong><i>ABCG2</i> variants were found to be ideal genetic biomarkers for both PK and PD characteristics of apixaban. <i>ABLIM2, F13A1</i> and <i>C3</i> were identified as potential candidate genes associated with inter-individual variability of apixaban. This study was registered on ClinicalTrials.gov NCT03259399.</p>","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"19 1","pages":"43-51"},"PeriodicalIF":3.9000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification of genetic biomarkers associated with pharmacokinetics and pharmacodynamics of apixaban in Chinese healthy volunteers.\",\"authors\":\"Guangyan Mu, Qiufen Xie, Zhiyan Liu, Hanxu Zhang, Xianmin Meng, Jinfang Song, Shuang Zhou, Zhe Wang, Zining Wang, Xia Zhao, Jie Jiang, Maoxing Liao, Jiachun Bao, Fan Zhang, Qian Xiang, Yimin Cui\",\"doi\":\"10.1080/17425255.2023.2184344\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Several <i>ABCG2</i> variants were associated with C<sub>max</sub> and AUC<sub>0-t</sub> of apixaban (p < 6.12 × 10<sup>-5</sup>) and also presented significant differences of anti-Xa<sub>3h</sub> activity and dPT<sub>3h</sub> according to different <i>ABCG2</i> genotypes (p < 0.05). Besides, <i>ABLIM2</i> variants were found to be associated with PK characteristics and <i>F13A1</i> and C3 variants were associated with PD characteristics of apixaban (p < 9.46 × 10<sup>-8</sup>).</p><p><strong>Conclusion: </strong><i>ABCG2</i> variants were found to be ideal genetic biomarkers for both PK and PD characteristics of apixaban. <i>ABLIM2, F13A1</i> and <i>C3</i> were identified as potential candidate genes associated with inter-individual variability of apixaban. This study was registered on ClinicalTrials.gov NCT03259399.</p>\",\"PeriodicalId\":12250,\"journal\":{\"name\":\"Expert Opinion on Drug Metabolism & Toxicology\",\"volume\":\"19 1\",\"pages\":\"43-51\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Opinion on Drug Metabolism & Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17425255.2023.2184344\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Opinion on Drug Metabolism & Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17425255.2023.2184344","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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.
期刊介绍：
Expert Opinion on Drug Metabolism & Toxicology (ISSN 1742-5255 [print], 1744-7607 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on all aspects of ADME-Tox. Each article is structured to incorporate the author’s own expert opinion on the scope for future development.
The Editors welcome:
Reviews covering metabolic, pharmacokinetic and toxicological issues relating to specific drugs, drug-drug interactions, drug classes or their use in specific populations; issues relating to enzymes involved in the metabolism, disposition and excretion of drugs; techniques involved in the study of drug metabolism and toxicology; novel technologies for obtaining ADME-Tox data.
Drug Evaluations reviewing the clinical, toxicological and pharmacokinetic data on a particular drug.
The audience consists of scientists and managers in the pharmaceutical industry, pharmacologists, clinical toxicologists and related professionals.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
