Laboratory of Pharmacology & Clinical Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100 Alexandroupolis, Greece.
Pharmacogenomics. 2010 Apr;11(4):493-6. doi: 10.2217/pgs.10.31.
Coumarinic oral anticoagulants are life-saving drugs, but are also one of the leading causes of drug-induced major bleeding events. Moreover, there is substantial individual variation in response to coumarinic oral anticoagulants caused by several factors including variations in the CYP2C9 and VKORC1 genes. Several retrospective and a few small prospective clinical studies have shown that polymorphisms in CYP2C9 and VKORC1 genes together account for 35-50% of the variability in warfarin initiation and maintenance dose requirements. Large randomized clinical trials are currently underway to further solidify the safety, clinical utility and cost-effectiveness of pharmacogenetic-guided dosing algorithms for warfarin, acenocoumarol and phenprocoumon. By 2020, coumarinic oral anticoagulant pharmacogenetic testing will be part of routine clinical practice in anticoagulant therapy.
香豆素类口服抗凝剂是救命药，但也是导致药物诱导的主要出血事件的主要原因之一。此外，由于多种因素，包括 CYP2C9 和 VKORC1 基因的变异，对香豆素类口服抗凝剂的反应存在很大的个体差异。几项回顾性和少数小型前瞻性临床研究表明，CYP2C9 和 VKORC1 基因的多态性共同解释了华法林起始和维持剂量需求的 35-50%的可变性。目前正在进行大型随机临床试验，以进一步证实华法林、醋硝香豆素和苯丙香豆素的基于遗传药理学的给药算法的安全性、临床实用性和成本效益。到 2020 年，香豆素类口服抗凝药的遗传药理学检测将成为抗凝治疗常规临床实践的一部分。
