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