香豆素类抗凝剂的药物遗传学指导剂量：华法林、醋硝香豆素和苯丙香豆素的算法
Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon.
作者信息
Verhoef Talitha I, Redekop William K, Daly Ann K, van Schie Rianne M F, de Boer Anthonius, Maitland-van der Zee Anke-Hilse
机构信息
Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht.
出版信息
Br J Clin Pharmacol. 2014 Apr;77(4):626-41. doi: 10.1111/bcp.12220.
Abstract
Coumarin derivatives, such as warfarin, acenocoumarol and phenprocoumon are frequently prescribed oral anticoagulants to treat and prevent thromboembolism. Because there is a large inter-individual and intra-individual variability in dose-response and a small therapeutic window, treatment with coumarin derivatives is challenging. Certain polymorphisms in CYP2C9 and VKORC1 are associated with lower dose requirements and a higher risk of bleeding. In this review we describe the use of different coumarin derivatives, pharmacokinetic characteristics of these drugs and differences amongst the coumarins. We also describe the current clinical challenges and the role of pharmacogenetic factors. These genetic factors are used to develop dosing algorithms and can be used to predict the right coumarin dose. The effectiveness of this new dosing strategy is currently being investigated in clinical trials.
摘要
香豆素衍生物，如华法林、醋硝香豆素和苯丙香豆素，是常用的口服抗凝剂，用于治疗和预防血栓栓塞。由于个体间和个体内剂量反应存在很大差异，且治疗窗较窄，使用香豆素衍生物进行治疗具有挑战性。细胞色素P450 2C9（CYP2C9）和维生素K环氧化物还原酶复合体1（VKORC1）的某些基因多态性与较低的剂量需求和较高的出血风险相关。在本综述中，我们描述了不同香豆素衍生物的使用、这些药物的药代动力学特征以及香豆素之间的差异。我们还描述了当前的临床挑战以及药物遗传学因素的作用。这些遗传因素被用于制定给药算法，并可用于预测合适的香豆素剂量。这种新给药策略的有效性目前正在临床试验中进行研究。
相似文献
1
Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon.香豆素类抗凝剂的药物遗传学指导剂量：华法林、醋硝香豆素和苯丙香豆素的算法
Br J Clin Pharmacol. 2014 Apr;77(4):626-41. doi: 10.1111/bcp.12220.
2
Pharmacogenetics of oral anticoagulants: a basis for dose individualization.口服抗凝剂的药物遗传学：剂量个体化的基础。
Clin Pharmacokinet. 2008;47(9):565-94. doi: 10.2165/00003088-200847090-00002.
3
Pharmacogenetic differences between warfarin, acenocoumarol and phenprocoumon.华法林、醋硝香豆素和苯丙香豆素之间的药物遗传学差异。
Thromb Haemost. 2008 Dec;100(6):1052-7.
4
Dosing algorithms for vitamin K antagonists across VKORC1 and CYP2C9 genotypes.维生素 K 拮抗剂在 VKORC1 和 CYP2C9 基因型中的给药算法。
J Thromb Haemost. 2017 Mar;15(3):465-472. doi: 10.1111/jth.13615. Epub 2017 Feb 17.
5
Patients benefit from genetics-guided coumarin anticoagulant therapy.患者受益于基于遗传学的香豆素类抗凝治疗。
Clin Pharmacol Ther. 2014 Jul;96(1):15-7. doi: 10.1038/clpt.2014.44.
6
Loading and maintenance dose algorithms for phenprocoumon and acenocoumarol using patient characteristics and pharmacogenetic data.基于患者特征和遗传药理学数据的苯丙香豆素和醋硝香豆素的负荷剂量和维持剂量算法。
Eur Heart J. 2011 Aug;32(15):1909-17. doi: 10.1093/eurheartj/ehr116. Epub 2011 Jun 2.
7
Pharmacogenetics and coumarin dosing--recalibrating expectations.药物遗传学与香豆素剂量——重新校准预期
N Engl J Med. 2013 Dec 12;369(24):2273-5. doi: 10.1056/NEJMp1314529.
8
Genotype-guided vs clinical dosing of warfarin and its analogues: meta-analysis of randomized clinical trials.基于基因型的华法林及其类似物与临床剂量给药：随机临床试验的荟萃分析。
JAMA Intern Med. 2014 Aug;174(8):1330-8. doi: 10.1001/jamainternmed.2014.2368.
9
The value of pharmacogenetic testing.药物遗传学检测的价值。
JAMA Intern Med. 2015 Feb;175(2):314. doi: 10.1001/jamainternmed.2014.7017.
10
The value of pharmacogenetic testing—reply.药物遗传学检测的价值——回复。
JAMA Intern Med. 2015 Feb;175(2):314-5. doi: 10.1001/jamainternmed.2014.7023.
引用本文的文献
1
Direct Oral Anticoagulants vs. Vitamin K Antagonists for Atrial Fibrillation in Cardiac Amyloidosis: A Systematic Review and Meta-analysis.直接口服抗凝剂与维生素K拮抗剂用于心脏淀粉样变性心房颤动的比较：一项系统评价和荟萃分析
Rev Cardiovasc Med. 2025 Mar 13;26(3):26948. doi: 10.31083/RCM26948. eCollection 2025 Mar.
2
Plant glycosides and glycosidases: classification, sources, and therapeutic insights in current medicine.植物糖苷和糖苷酶：当前医学中的分类、来源及治疗见解
Glycoconj J. 2025 Apr;42(2):107-124. doi: 10.1007/s10719-025-10180-3. Epub 2025 Feb 24.
3
A Case of Unexplained Warfarin Resistance: A Case Report and Literature Review.一例不明原因华法林抵抗病例报告及文献综述
J Tehran Heart Cent. 2023 Oct;18(4):302-306. doi: 10.18502/jthc.v18i4.14831.
4
Cardiovascular precision medicine - A pharmacogenomic perspective.心血管精准医学——药物基因组学视角
Camb Prism Precis Med. 2023 Jun 29;1:e28. doi: 10.1017/pcm.2023.17. eCollection 2023.
5
A bimolecular modification strategy for developing long-lasting bone anabolic aptamer.一种用于开发长效骨合成适配体的双分子修饰策略。
Mol Ther Nucleic Acids. 2023 Nov 10;34:102073. doi: 10.1016/j.omtn.2023.102073. eCollection 2023 Dec 12.
6
Nonlinear Machine Learning in Warfarin Dose Prediction: Insights from Contemporary Modelling Studies.华法林剂量预测中的非线性机器学习：当代建模研究的见解
J Pers Med. 2022 Apr 29;12(5):717. doi: 10.3390/jpm12050717.
7
Ethnic Diversity and Warfarin Pharmacogenomics.种族多样性与华法林药物基因组学
Front Pharmacol. 2022 Apr 4;13:866058. doi: 10.3389/fphar.2022.866058. eCollection 2022.
8
Dry Needling and Antithrombotic Drugs.干针疗法和抗血栓药物。
Pain Res Manag. 2022 Jan 7;2022:1363477. doi: 10.1155/2022/1363477. eCollection 2022.
9
The influence of excessive consumption of liquorice on phenprocoumon (Marcumar®): a case report.甘草过量对苯丙香豆素（华法令）的影响：一例报告。
J Int Med Res. 2021 Nov;49(11):3000605211049649. doi: 10.1177/03000605211049649.
10
The Effects of Osteoporotic and Non-osteoporotic Medications on Fracture Risk and Bone Mineral Density.骨质疏松症和非骨质疏松症药物对骨折风险和骨密度的影响。
Drugs. 2021 Nov;81(16):1831-1858. doi: 10.1007/s40265-021-01625-8. Epub 2021 Nov 1.
本文引用的文献
1
Influence of VKORC1 gene polymorphisms on the effect of oral vitamin K supplementation in over-anticoagulated patients.维生素K环氧化物还原酶复合体亚单位1（VKORC1）基因多态性对口服维生素K补充剂在抗凝过度患者中疗效的影响。
J Thromb Thrombolysis. 2014 Apr;37(3):338-44. doi: 10.1007/s11239-013-0947-3.
2
Reversal of novel oral anticoagulants in patients with major bleeding.新型口服抗凝剂致大出血患者的逆转。
J Thromb Thrombolysis. 2013 Apr;35(3):391-8. doi: 10.1007/s11239-013-0885-0.
3
Novel oral anticoagulants in atrial fibrillation: a meta-analysis of large, randomized, controlled trials vs warfarin.新型口服抗凝剂在心房颤动中的应用：与华法林相比的大型随机对照试验的荟萃分析。
Clin Cardiol. 2013 Feb;36(2):61-7. doi: 10.1002/clc.22081. Epub 2013 Jan 21.
4
Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial.阿哌沙班药效学剂量算法与常规护理在静脉血栓栓塞性疾病患者启动口服抗凝治疗中的应用效率和效果比较：一项随机对照试验研究方案。
Trials. 2012 Dec 13;13:239. doi: 10.1186/1745-6215-13-239.
5
Development of a pharmacogenetic-guided warfarin dosing algorithm for Puerto Rican patients.开发一种基于遗传药理学的华法林剂量算法，用于波多黎各患者。
Pharmacogenomics. 2012 Dec;13(16):1937-50. doi: 10.2217/pgs.12.171.
6
Evaluation of the effect of genetic variations in GATA-4 on the phenprocoumon and acenocoumarol maintenance dose.评价 GATA-4 基因变异对苯丙香豆素和醋硝香豆素维持剂量的影响。
Pharmacogenomics. 2012 Dec;13(16):1917-23. doi: 10.2217/pgs.12.174.
7
Creating a genotype-based dosing algorithm for acenocoumarol steady dose.建立基于基因型的华法林稳定剂量给药算法。
Thromb Haemost. 2013 Jan;109(1):146-53. doi: 10.1160/TH12-08-0631. Epub 2012 Nov 29.
8
Long-term anticoagulant effects of CYP2C9 and VKORC1 genotypes in phenprocoumon users.苯丙香豆素使用者中CYP2C9和VKORC1基因的长期抗凝作用。
J Thromb Haemost. 2012 Dec;10(12):2610-2. doi: 10.1111/jth.12007.
9
Estimation of the warfarin dose with a pharmacogenetic refinement algorithm in Chinese patients mainly under low-intensity warfarin anticoagulation.在中国患者中，主要在低强度华法林抗凝治疗下，使用药物遗传学细化算法估算华法林剂量。
Thromb Haemost. 2012 Dec;108(6):1132-40. doi: 10.1160/TH12-05-0362. Epub 2012 Sep 26.
10
Cost-effectiveness of pharmacogenetics in anticoagulation: international differences in healthcare systems and costs.药物遗传学在抗凝治疗中的成本效益：医疗体系和成本的国际差异。
Pharmacogenomics. 2012 Sep;13(12):1405-17. doi: 10.2217/pgs.12.124.
Zotero 插件