Effect of CYP2C9-VKORC1 interaction on warfarin stable dosage and its predictive algorithm

This study aimed to identify the effect of CYP2C9–VKORC1 interaction on warfarin dosage requirement and its predictive algorithm by investigating four populations. Generalized linear model was used to evaluate the relationship between the interaction and warfarin stable dosage (WSD), whereas multipl...

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Bibliographic Details
Published in:Journal of clinical pharmacology Vol. 55; no. 3; pp. 251 - 257
Main Authors: Li, Xi, Liu, Rong, Yan, Han, Tang, Jie, Yin, Ji-Ye, Mao, Xiao-Yuan, Yang, Fang, Luo, Zhi-Yin, Tan, Sheng-Lan, He, Hui, Chen, Xiao-Ping, Liu, Zhao-Qian, Li, Zhi, Zhou, Hong-Hao, Zhang, Wei
Format: Journal Article
Language:English
Published: England Blackwell Publishing Ltd 01.03.2015
American College of Clinical Pharmacology
Wiley Subscription Services, Inc
Subjects:
Adolescent
Adult
African Continental Ancestry Group - genetics
Aged
Aged, 80 and over
Algorithms
Anticoagulants - administration & dosage
Anticoagulants - adverse effects
Anticoagulants - pharmacokinetics
Asian Continental Ancestry Group - genetics
Blood Coagulation - drug effects
Chi-Square Distribution
Child
Cytochrome P-450 CYP2C9 - genetics
Cytochrome P-450 CYP2C9 - metabolism
Drug Dosage Calculations
Drug Monitoring - methods
epistasis
European Continental Ancestry Group - genetics
Female
Gene Frequency
Genotype
Health risk assessment
Humans
International Normalized Ratio
Linear Models
Male
Middle Aged
Models, Biological
Pharmacogenetics
Phenotype
racial difference
Regression analysis
Risk Factors
single nucleotide polymorphism
Vitamin K Epoxide Reductases - genetics
Vitamin K Epoxide Reductases - metabolism
warfarin
Warfarin - administration & dosage
Warfarin - adverse effects
Warfarin - pharmacokinetics
Young Adult
racial difference
algorithms
epistasis
single nucleotide polymorphism
warfarin
ISSN:0091-2700, 1552-4604, 1552-4604
Online Access:Get full text
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Summary:This study aimed to identify the effect of CYP2C9–VKORC1 interaction on warfarin dosage requirement and its predictive algorithm by investigating four populations. Generalized linear model was used to evaluate the relationship between the interaction and warfarin stable dosage (WSD), whereas multiple linear regression analysis was applied to construct the WSD predictive algorithm. To evaluate the effect of CYP2C9–VKORC1 interaction on the predictive algorithms, we compared the algorithms with and without the interaction. The interaction was significantly associated with WSD in the Chinese and White cohorts (P values < 0.05). In the algorithms that considered the interaction, the predictive success rates improved by only 0.12% in the Chinese patients and by a maximum of 0.02% in the White patients under four different CYP2C9 classifications. Thus, VKORC1–CYP2C9 interaction can affect WSD. However, the discrepancy between the predictive results obtained using the predictive algorithm with and without CYP2C9–VKORC1 interaction was negligible and can therefore be disregarded.
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ISSN:0091-2700
1552-4604
1552-4604
DOI:10.1002/jcph.392