Evidence map›Paper›PMID 31037455›Full record

ArticleEuropean journal of clinical pharmacology2019

Relationship between warfarin dosage and international normalized ratio: a dose-response analysis and evaluation based on multicenter data.

Ling Xue, Yuzhen Zhang, Cheng Xie, Ling Zhou, Linsheng Liu, Haiyan Zhang, Lianhong Xu, Hongtao Song, Meiqin Lin, Hanfan Qiu and 10 more

Abstract readMulticenter Study
PubMed Publisher
In one paragraph

Article in European journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 9 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 9 institutions in 1 country.

Ling XueDepartment of Clinical Pharmacology, the First Affiliated Hospital of Soochow University, Suzhou, China.
Yuzhen ZhangDepartment of Cardiology, the First Affiliated Hospital of Soochow University, Suzhou, China.
Cheng XieDepartment of Clinical Pharmacology, the First Affiliated Hospital of Soochow University, Suzhou, China.
Ling ZhouDepartment of Clinical Pharmacology, the First Affiliated Hospital of Soochow University, Suzhou, China.
Linsheng LiuDepartment of Clinical Pharmacology, the First Affiliated Hospital of Soochow University, Suzhou, China.
Haiyan ZhangDepartment of Pharmacy, the Affiliated Wujin Hospital of Jiangsu University, Changzhou, China.
Lianhong XuDepartment of Clinical Laboratory, the Affiliated Wujin Hospital of Jiangsu University, Changzhou, China.
Hongtao SongDepartment of pharmacy, Fuzhou General Hospital, Fuzhou, China.
Meiqin LinDepartment of pharmacy, Fuzhou General Hospital, Fuzhou, China.
Hanfan QiuDepartment of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
Junrong ZhuDepartment of Clinical Pharmacology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Yubing ZhuDepartment of Clinical Pharmacology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Jianjun ZouDepartment of Clinical Pharmacology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Wenfang ZhuangDepartment of Laboratory Medicine, East hospital of Yangpu district, Shanghai, China.
Binbin XuanDepartment of Laboratory Medicine, Tongren Hospital, Shanghai Jiao Tong University School Of Medicine, Shanghai, China.
Yanhong ChenDepartment of Laboratory Medicine, Tongren Hospital, Shanghai Jiao Tong University School Of Medicine, Shanghai, China.
Yingchao FanDepartment of Laboratory Medicine, East hospital of Yangpu district, Shanghai, China.
Di WuDepartment of Clinical Pharmacy, the First Affiliated Hospital of Kunming Medical University, Kunming, China.
Zhenya ShenDepartment of Cardiovascular Surgery, the First Affiliated Hospital of Soochow University, Suzhou, China. uuzyshen@sina.com.
Liyan MiaoDepartment of Clinical Pharmacology, the First Affiliated Hospital of Soochow University, Suzhou, China. miaolysuzhou@163.com.
Soochow University · CNFirst Affiliated Hospital of Soochow University · CNNanjing Medical University · CNFuzhou General Hospital of Nanjing Military Command · CNJiangsu University · CNFirst Affiliated Hospital of Kunming Medical University · CNFujian Medical University · CNShanghai Jiao Tong University · CNTongren Hospital · CN

Funding

National Key New Drug Creation Special Programs 2017ZX09304-021People's Livelihood Science and Technology Foundation of Suzhou Science and Technology Bureau SYS201736Suzhou Key Laboratory of Drug Clinical Research and Personalized Medicine SZS201719Young Scientists Fund 81503140Young Scientists Fund 81700298Young Scientists Fund 81803628
6 · The paper itself

Abstract

purposeThe 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.

methodsClinical 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.

resultsThe 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%.

conclusionA 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.

Indexed as

International Normalized RatioModels, BiologicalAdultAgedAged, 80 and overAnticoagulantsDose-Response Relationship, DrugFemaleHumansMaleMiddle AgedWarfarinAnticoagulantsWarfarinDose–response modelInternational normalized ratioPharmacogenomicsWarfarin

Identifiers

PMID31037455
OpenAlexW2943502855

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.