Relationship between warfarin dosage and international normalized ratio: a dose–response analysis and evaluation based on multicenter data.
Purpose: The objectives of the study were to establish a dose–response model for warfarin based on the relationship between daily warfarin dose and international normalized ratio (INR) and to evaluate the stability and reliability of the established model using external data. Methods: Clinical data...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 75; no. 6; pp. 785 - 795 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | equations & formulas research tables/charts Journal Article |
| Publicado: |
Springer Nature
Jun2019
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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=136694095&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 136694095 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Jun2019 vid: 75 iid: 6 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 136694095 136694095 136694095 10.1007/s00228-019-02655-8 136694095 ppf: 785 ppct: 10 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Relationship between warfarin dosage and international normalized ratio: a dose–response analysis and evaluation based on multicenter data. aug: au: Xue, Ling Zhang, Yuzhen Xie, Cheng Zhou, Ling Liu, Linsheng Zhang, Haiyan Xu, Lianhong Song, Hongtao Lin, Meiqin Qiu, Hanfan Zhu, Junrong Zhu, Yubing Zou, Jianjun Zhuang, Wenfang Xuan, Binbin Chen, Yanhong Fan, Yingchao Wu, Di Shen, Zhenya Miao, Liyan affil: Department of Clinical Pharmacology, the First Affiliated Hospital of Soochow University, Suzhou, China sug: subj: Warfarin Administration and Dosage International Normalized Ratio Dose-Response Relationship, Drug Pharmacogenetics Human Outpatients Multicenter Studies Genotype Reliability Stability Goodness of Fit Chi Square Test Nonparametric Statistics Multivariate Statistics Linear Regression Descriptive Statistics Amiodarone Administration and Dosage Models, Biological Fat Free Mass ab: Purpose: The objectives of the study were to establish a dose–response model for warfarin based on the relationship between daily warfarin dose and international normalized ratio (INR) and to evaluate the stability and reliability of the established model using external data. Methods: Clinical data were recorded from 676 outpatients with a steady-state warfarin dosage. Demographic characteristics, concomitant medications, daily dosage of warfarin, CYP2C9 and VKORC1 genotypes, and INR were recorded. Data analysis based on the Michaelis–Menten equation to describe the relationship between daily warfarin dose and INR was performed using NONMEM. The reliability and stability of the final model were evaluated using goodness-of-fit plots, resampling techniques with a nonparametric bootstrap, and external data. Results: The daily warfarin dose and INR were described by a more pharmacologically expressive model than multivariate linear regression (MLR) model. The population standard value of Km was 3.56 mg, and the Hill coefficient was 0.512, with individual variabilities of 53.1% and 55.9%, respectively. CYP2C9 *1/*3, VKORC1 AA, concomitant amiodarone, and nonheart valve replacement reduced the warfarin Km by 30.4%, 74.3%, 34.5%, and 39.4%, respectively. The Km value decreased with age and increased with fat free mass (FFM). INR prediction error (73.0%) of the external datasets was within ± 20%. Conclusion: A dose–response model of warfarin was established based on the relationship between daily warfarin dose and INR. Expected genotype effects on Km and demographic characteristics were confirmed. The model has the potential to be a powerful tool for individualized warfarin therapy for Chinese outpatients. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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