Quantitative Comparison of the Predictive Accuracy of Warfarin Pharmacogenetic Dosing Algorithms Derived From Population Data of Different Ethnicities in the Chinese Population.

IF 2.3 4区 医学
Dongyun Nan, Shaoke Li, Yi Wang, Yiqun Cai, Bo Liu, Jialing Peng, Jiexin Deng
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Abstract

This study systematically evaluated the predictive performance of 10 international warfarin dosing algorithms (originating from the United States, China, Singapore, Thailand, India, United Kingdom, Japan, and South Korea) in 87 Chinese patients, aiming to identify optimal algorithms for warfarin dose optimization. Clinical and genetic data were analyzed using mean dose error (MDE) and ideal dose prediction (IDP) rate metrics, with sensitivity analysis stratifying patients into low-dose (≤14 mg/week, n = 21), medium-dose (14-21 mg/week, n = 43), and high-dose (≥21 mg/week, n = 23) groups based on actual weekly maintenance dose (mean: 18.9 ± 8.8 mg/week). Results revealed significant variation in MDEs (-6.6 to 11.3 mg/week) across algorithms. The Chinese-developed Huang algorithm and Thai-developed Sangviroon algorithm demonstrated superior overall accuracy, both achieving MDEs <1 mg/week and IDPs >40%. In medium-dose patients, their performance was particularly robust (Huang IDP: 65.1%; Sangviroon IDP: 74.4%). However, both algorithms showed limitations at dose extremes: they overestimated doses in 90.48% of low-dose patients and underestimated doses in 60.9%-65.2% of high-dose patients. This evidence indicates that region-specific algorithms (Huang and Sangviroon) outperform internationally recommended models (e.g., IWPC/Gage endorsed by CPIC) for warfarin dosing in Chinese populations. Locally derived algorithms may thus offer greater clinical utility despite current international guidelines.

基于中国不同种族人群数据的华法林药物遗传给药算法预测准确性的定量比较。
本研究系统评估了10种国际华法林剂量算法(分别来自美国、中国、新加坡、泰国、印度、英国、日本和韩国)在87例中国患者中的预测性能,旨在确定华法林剂量优化的最佳算法。采用平均剂量误差(MDE)和理想剂量预测(IDP)率指标对临床和遗传学数据进行分析,并根据每周实际维持剂量(平均值:18.9±8.8 mg/周)将患者分为低剂量组(≤14 mg/周,n = 21)、中剂量组(14-21 mg/周,n = 43)和高剂量组(≥21 mg/周,n = 23)。结果显示,不同算法的MDEs差异显著(-6.6至11.3 mg/周)。中国开发的Huang算法和泰国开发的Sangviroon算法显示出优越的总体精度,两者都达到MDEs 40%。在中剂量患者中,它们的表现尤其稳健(Huang IDP: 65.1%; Sangviroon IDP: 74.4%)。然而,这两种算法在剂量极值时都存在局限性:它们在90.48%的低剂量患者中高估了剂量,在60.9%-65.2%的高剂量患者中低估了剂量。这一证据表明,区域特定算法(Huang和Sangviroon)在中国人群华法林给药方面优于国际推荐的模型(例如,CPIC认可的IWPC/Gage)。尽管目前的国际准则,本地衍生的算法可能因此提供更大的临床效用。
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来源期刊
Journal of Clinical Pharmacology
Journal of Clinical Pharmacology PHARMACOLOGY & PHARMACY-
自引率
3.40%
发文量
0
期刊介绍: The Journal of Clinical Pharmacology (JCP) is a Human Pharmacology journal designed to provide physicians, pharmacists, research scientists, regulatory scientists, drug developers and academic colleagues a forum to present research in all aspects of Clinical Pharmacology. This includes original research in pharmacokinetics, pharmacogenetics/pharmacogenomics, pharmacometrics, physiologic based pharmacokinetic modeling, drug interactions, therapeutic drug monitoring, regulatory sciences (including unique methods of data analysis), special population studies, drug development, pharmacovigilance, womens’ health, pediatric pharmacology, and pharmacodynamics. Additionally, JCP publishes review articles, commentaries and educational manuscripts. The Journal also serves as an instrument to disseminate Public Policy statements from the American College of Clinical Pharmacology.
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