Optimisation of warfarin-dosing algorithms for Han Chinese patients with CYP2C9*13 variants.
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,...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 79; no. 10; pp. 1315 - 1321 |
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| Autores principales: | , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Oct2023
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=171951759&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 171951759 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Oct2023 vid: 79 iid: 10 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 171951759 164956831 171951759 171951759 10.1007/s00228-023-03540-1 171951759 ppf: 1315 ppct: 6 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Optimisation of warfarin-dosing algorithms for Han Chinese patients with CYP2C9*13 variants. aug: au: Wang, Dongxu Wu, Hualan Zhang, Qing Zhou, Xiaoyue An, Yang Zhao, Anxu Chong, Jia Wang, Shuanghu Wang, Fang Yang, Jiefu Dai, Dapeng Chen, Hao affil: https://ror.org/02jwb5s28 Cardiovascular Department, Beijing Hospital, National Centre of Gerontology, 100730, Beijing, China sug: subj: Genotype Algorithms Evaluation Cytochrome P-450 Enzyme System Warfarin Administration and Dosage Atrial Fibrillation Drug Therapy Polymorphism, Genetic Chinese Persons Pharmacogenetics China Human Male Alleles Quantitative Studies Drug Efficacy Patient Safety Sequence Analysis Descriptive Statistics Male ab: 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. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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