Optimisation of warfarin-dosing algorithms for Han Chinese patients with CYP2C913 variants

• Published in: European journal of clinical pharmacology 2023-10, Vol.79 (10), p.1315-1320
• Main Authors: Wang, Dongxu, Wu, Hualan, Zhang, Qing, Zhou, Xiaoyue, An, Yang, Zhao, Anxu, Chong, Jia, Wang, Shuanghu, Wang, Fang, Yang, Jiefu, Dai, Dapeng, Chen, Hao
• Format: Article
• Language: English
• Subjects: Algorithms; Biomedical and Life Sciences; Biomedicine; Dosage; Genotypes; Pharmacology/Toxicology; Warfarin
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-023-03540-1

Background Existing pharmacogenetic algorithms cannot fully explain warfarin dose variability in all patients. CYP2C9*13 is an important allelic variant in the Han Chinese population. However, adjustment of warfarin dosing in CYP2C9*13 variant carriers remains unclear. To the best of our knowledge, this study is the first to assess the effects of adjusting warfarin dosages in Han Chinese patients harbouring CYP2C9*13 variants. Methods In total, 971 warfarin-treated Han Chinese patients with atrial fibrillation were enrolled in this study. Clinical data were collected, and CYP2C9*2 , *3 , *13 and VKORC1-1639 G  >  A variants were genotyped. We quantitatively analysed the effect of CYP2C9*13 on warfarin maintenance dose and provided multiplicative adjustments for CYP2C9*13 using validated pharmacogenetic algorithms. Results Approximately 0.6% of the Han Chinese population carried CYP2C9*13 variant, and the genotype frequency was between those of CYP2C9*2 and CYP2C9*3 . The warfarin maintenance doses were significantly reduced in CYP2C9*13 carriers. When CYP2C9*13 variants were not considered, the pharmacogenetic algorithms overestimated warfarin maintenance doses by 1.03–1.16 mg/d on average. The actual warfarin dose in CYP2C9*13 variant carriers was approximately 40% lower than the algorithm-predicted dose. Adjusting the warfarin-dosing algorithm according to the CYP2C9*13 allele could reduce the dose prediction error. Conclusion Our study showed that the algorithm-predicted doses should be lowered for CYP2C9*13 carriers. Inclusion of the CYP2C9*13 variant in the warfarin-dosing algorithm tends to predict the warfarin maintenance dose more accurately and improves the efficacy and safety of warfarin administration in Han Chinese patients.