临床药物基因组学实施联盟 (CPIC) CYP2C9 和 HLA-B 基因型与苯妥英钠剂量指南：2020 年更新。
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing: 2020 Update.
机构信息
Department of Pharmacy Practice & Science, University of Arizona College of Pharmacy, Tucson, Arizona, USA.
Sarver Heart Center, University of Arizona College of Medicine, Tucson, Arizona, USA.
出版信息
Clin Pharmacol Ther. 2021 Feb;109(2):302-309. doi: 10.1002/cpt.2008. Epub 2020 Sep 6.
Abstract
Phenytoin is an antiepileptic drug with a narrow therapeutic index and large interpatient pharmacokinetic variability, partly due to genetic variation in CYP2C9. Furthermore, the variant allele HLA-B*15:02 is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in response to phenytoin treatment. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for the use of phenytoin based on CYP2C9 and/or HLA-B genotypes (updates on cpicpgx.org).
摘要
苯妥英是一种抗癫痫药物，治疗指数较窄，个体间药代动力学变异性较大，部分原因是 CYP2C9 的遗传变异。此外，变异等位基因 HLA-B*15:02 与苯妥英治疗后史蒂文斯-约翰逊综合征和中毒性表皮坏死松解症的风险增加相关。我们总结了已发表文献中的证据，支持这些关联，并根据 CYP2C9 和/或 HLA-B 基因型提供苯妥英使用的治疗建议（在 cpicpgx.org 上更新）。
相似文献
1
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing: 2020 Update.临床药物基因组学实施联盟 (CPIC) CYP2C9 和 HLA-B 基因型与苯妥英钠剂量指南：2020 年更新。
Clin Pharmacol Ther. 2021 Feb;109(2):302-309. doi: 10.1002/cpt.2008. Epub 2020 Sep 6.
2
Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing.临床药物基因组学实施联盟关于CYP2C9和HLA - B基因型与苯妥英钠给药的指南。
Clin Pharmacol Ther. 2014 Nov;96(5):542-8. doi: 10.1038/clpt.2014.159. Epub 2014 Aug 6.
3
An update on CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects.CYP2C9 多态性与苯妥英代谢更新：不良效应相关影响。
Expert Opin Drug Metab Toxicol. 2020 Aug;16(8):723-734. doi: 10.1080/17425255.2020.1780209. Epub 2020 Jul 16.
4
Associations between HLA class I and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population.泰国人群中HLA I类和细胞色素P450 2C9基因多态性与苯妥英相关严重皮肤不良反应之间的关联
Pharmacogenet Genomics. 2016 May;26(5):225-34. doi: 10.1097/FPC.0000000000000211.
5
Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing.临床药物遗传学实施联盟指南：HLA-B 基因型与卡马西平剂量。
Clin Pharmacol Ther. 2013 Sep;94(3):324-8. doi: 10.1038/clpt.2013.103. Epub 2013 May 21.
7
Clinical Pharmacogenetics Implementation Consortium Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update.临床药物遗传学实施联盟指南：人类白细胞抗原基因型与卡马西平和奥卡西平的应用：2017 更新版。
Clin Pharmacol Ther. 2018 Apr;103(4):574-581. doi: 10.1002/cpt.1004. Epub 2018 Feb 2.
8
Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese.汉族人群芳香族抗癫痫药物诱导的 Stevens-Johnson 综合征和中毒性表皮坏死松解症的常见风险等位基因。
Pharmacogenomics. 2010 Mar;11(3):349-56. doi: 10.2217/pgs.09.162.
9
Association of CYP2C9*3 with phenytoin-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: A systematic review and meta-analysis.CYP2C9*3与苯妥英钠诱发的史蒂文斯-约翰逊综合征及中毒性表皮坏死松解症的关联：一项系统评价与荟萃分析
J Clin Pharm Ther. 2018 Jun;43(3):408-413. doi: 10.1111/jcpt.12660. Epub 2017 Dec 23.
10
Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing.临床药物遗传学实施联盟 HLA-B 基因型和别嘌醇剂量指南。
Clin Pharmacol Ther. 2013 Feb;93(2):153-8. doi: 10.1038/clpt.2012.209. Epub 2012 Oct 17.
引用本文的文献
1
Drug hypersensitivity reactions in children in clinical practice: A WAO Statement.临床实践中儿童药物过敏反应：世界过敏组织声明
World Allergy Organ J. 2025 Aug 29;18(9):101087. doi: 10.1016/j.waojou.2025.101087. eCollection 2025 Sep.
2
Role of pharmacogenomics for prevention of hypersensitivity reactions induced by aromatic antiseizure medications.药物基因组学在预防芳香族抗癫痫药物引起的过敏反应中的作用。
Front Pharmacol. 2025 Aug 12;16:1640401. doi: 10.3389/fphar.2025.1640401. eCollection 2025.
3
Key informant perspectives on pharmacogenomic (PGx) testing for antidepressant prescribing in primary care in Ontario, Canada: a qualitative description study.加拿大安大略省基层医疗中抗抑郁药物处方的药物基因组学（PGx）检测的关键信息提供者观点：一项定性描述研究
BMJ Open. 2025 Aug 27;15(8):e091562. doi: 10.1136/bmjopen-2024-091562.
4
Next-Generation Approaches in Sports Medicine: The Role of Genetics, Omics, and Digital Health in Optimizing Athlete Performance and Longevity-A Narrative Review.运动医学的下一代方法：遗传学、组学和数字健康在优化运动员表现和寿命方面的作用——一篇叙述性综述。
Life (Basel). 2025 Jun 27;15(7):1023. doi: 10.3390/life15071023.
5
Promoter Variable Number Tandem Repeat Polymorphism in a Dominican Population: Exploring Differences with Genetic Ancestry.多米尼加人群中启动子可变数目串联重复序列多态性：探索与遗传血统的差异
Genes (Basel). 2025 Apr 30;16(5):540. doi: 10.3390/genes16050540.
6
Implementing Pre-Emptive Pharmacogenetics: Impact of Early Pharmacogenetic Screening in a Pediatric Oncology Cohort of 1,151 Subjects.实施先发制药物遗传学：1151名受试者的儿科肿瘤队列中早期药物遗传学筛查的影响
Clin Pharmacol Ther. 2025 Aug;118(2):438-448. doi: 10.1002/cpt.3685. Epub 2025 May 7.
7
The association between the number of HLA risk alleles and drug allergy and its implications for HLA screening - a case-control study.HLA风险等位基因数量与药物过敏之间的关联及其对HLA筛查的意义——一项病例对照研究。
Pharmacogenomics J. 2025 Feb 18;25(2):1. doi: 10.1038/s41397-025-00362-5.
8
Pharmacogenetics: Opportunities for the Research Program and Other Large Data Sets to Advance the Field.药物遗传学：研究项目及其他大型数据集推动该领域发展的机遇
Annu Rev Pharmacol Toxicol. 2025 Jan;65(1):111-130. doi: 10.1146/annurev-pharmtox-061724-080718.
9
Pharmacogenomic profiling of the South Korean population: Insights and implications for personalized medicine.韩国人群的药物基因组学分析：对个性化医疗的见解与启示。
Front Pharmacol. 2024 Dec 3;15:1476765. doi: 10.3389/fphar.2024.1476765. eCollection 2024.
10
Decoding Pharmacogenomic Test Interpretation and Application to Patient Care.解读药物基因组学检测结果及其在患者护理中的应用。
J Am Coll Clin Pharm. 2024 Jun;7(6):581-588. doi: 10.1002/jac5.1958. Epub 2024 May 8.
本文引用的文献
1
Allele frequency net database (AFND) 2020 update: gold-standard data classification, open access genotype data and new query tools.等位基因频率净数据库 (AFND) 2020 更新：金标准数据分类、开放获取基因型数据和新查询工具。
Nucleic Acids Res. 2020 Jan 8;48(D1):D783-D788. doi: 10.1093/nar/gkz1029.
2
Nonlinear protein binding of phenytoin in clinical practice: Development and validation of a mechanistic prediction model.临床实践中苯妥英的非线性蛋白结合：机制预测模型的建立与验证。
Br J Clin Pharmacol. 2019 Oct;85(10):2360-2368. doi: 10.1111/bcp.14053. Epub 2019 Aug 7.
3
A Screening Test for in a Large United States Patient Cohort Identifies Broader Risk of Carbamazepine-Induced Adverse Events.在美国一个大型患者队列中进行的一项筛查试验发现卡马西平诱导的不良事件风险范围更广。
Front Pharmacol. 2019 Mar 26;10:149. doi: 10.3389/fphar.2019.00149. eCollection 2019.
4
Association of cutaneous adverse drug reactions due to antiepileptic drugs with HLA alleles in a North Indian population.在印度北部人群中，与抗癫痫药物相关的皮肤不良反应与 HLA 等位基因有关。
Seizure. 2019 Mar;66:99-103. doi: 10.1016/j.seizure.2019.02.011. Epub 2019 Feb 20.
5
Applications of Immunopharmacogenomics: Predicting, Preventing, and Understanding Immune-Mediated Adverse Drug Reactions.免疫药理基因组学的应用：预测、预防和理解免疫介导的药物不良反应。
Annu Rev Pharmacol Toxicol. 2019 Jan 6;59:463-486. doi: 10.1146/annurev-pharmtox-010818-021818. Epub 2018 Aug 22.
6
Clinical Pharmacogenetics Implementation Consortium Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update.临床药物遗传学实施联盟指南：人类白细胞抗原基因型与卡马西平和奥卡西平的应用：2017 更新版。
Clin Pharmacol Ther. 2018 Apr;103(4):574-581. doi: 10.1002/cpt.1004. Epub 2018 Feb 2.
7
The Pharmacogene Variation (PharmVar) Consortium: Incorporation of the Human Cytochrome P450 (CYP) Allele Nomenclature Database.药物基因变异（PharmVar）联盟：纳入人类细胞色素 P450（CYP）等位基因命名数据库。
Clin Pharmacol Ther. 2018 Mar;103(3):399-401. doi: 10.1002/cpt.910. Epub 2017 Nov 14.
8
Phenome-wide scanning identifies multiple diseases and disease severity phenotypes associated with HLA variants.全表型扫描识别出与HLA变异相关的多种疾病及疾病严重程度表型。
Sci Transl Med. 2017 May 10;9(389). doi: 10.1126/scitranslmed.aai8708.
9
Influence of genetic and non-genetic factors on phenytoin-induced severe cutaneous adverse drug reactions.遗传和非遗传因素对苯妥英钠所致严重皮肤药物不良反应的影响。
Eur J Clin Pharmacol. 2017 Jul;73(7):855-865. doi: 10.1007/s00228-017-2250-2. Epub 2017 Apr 8.
10
Therapeutic Index Estimation of Antiepileptic Drugs: A Systematic Literature Review Approach.抗癫痫药物的治疗指数评估：一种系统文献综述方法
Clin Neuropharmacol. 2016 Sep-Oct;39(5):232-40. doi: 10.1097/WNF.0000000000000172.
Zotero 插件