Deng Jiexin, Wang Yi, An Xiaokang
School of Nursing and Health, Henan University, Kaifeng, China.
Department of Thoracic and Cardiovascular Surgery, Huaihe Hospital of Henan University, Kaifeng, China.
J Clin Pharmacol. 2023 May;63(5):569-582. doi: 10.1002/jcph.2197. Epub 2023 Jan 12.
Warfarin has a long record of safe and effective clinical use, and it remains one of the most commonly prescribed drugs for the prevention and treatment of thromboembolic conditions even in the era of direct oral anticoagulants. To address its large interindividual variability and narrow therapeutic window, the Clinical Pharmacogenetics Implementation Consortium has recommended using pharmacogenetic dosing algorithms, such as the ones developed by the International Warfarin Pharmacogenetics Consortium (IWPC) and by Gage et al, to dose warfarin when genotype information is available. In China, dosing algorithms based on local patient populations have been developed and evaluated for predictive accuracy of warfarin maintenance doses. In this study, percentage deviations of doses predicted by 15 Chinese dosing algorithms from that by IWPC and Gage algorithms were systematically evaluated to understand the differences between Chinese and Western algorithms. In general, dose predictions by Chinese dosing algorithms tended to be lower than those predicted by IWPC or Gage algorithms for the most prevalent VKORC1 and CYP2C9 genotypes in the Chinese population. The extent of negative prediction deviation appeared to be largest in the younger age group with smaller body weight. Our findings are consistent with previous reports that Asians have a higher sensitivity to warfarin and require lower doses than Western populations.
华法林在临床应用中有着长期安全有效的记录,即使在直接口服抗凝剂时代,它仍然是预防和治疗血栓栓塞性疾病最常用的处方药之一。为了解决其个体间差异大以及治疗窗窄的问题,临床药物基因组学实施联盟推荐在有基因型信息时,使用药物基因组学给药算法,如国际华法林药物基因组学联盟(IWPC)和盖奇等人开发的算法来确定华法林的剂量。在中国,已经开发并评估了基于当地患者群体的给药算法对华法林维持剂量的预测准确性。在本研究中,系统评估了15种中国给药算法预测的剂量与IWPC和盖奇算法预测的剂量之间的百分比偏差,以了解中西算法之间的差异。总体而言,对于中国人群中最常见的VKORC1和CYP2C9基因型,中国给药算法预测的剂量往往低于IWPC或盖奇算法预测的剂量。负预测偏差的程度在体重较轻的年轻人群中似乎最大。我们的研究结果与之前的报道一致,即亚洲人对华法林的敏感性高于西方人,所需剂量低于西方人群。