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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Vydáno v:	Journal of clinical pharmacology Ročník 55; číslo 3; s. 251 - 257
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Blackwell Publishing Ltd 01.03.2015 American College of Clinical Pharmacology Wiley Subscription Services, Inc
Témata:	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
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Shrnutí:	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.
Bibliografie:	ArticleID:JCPH392 istex:FC5189BEB02F6E8DFB1DF329C51688B85EBFD1E3 ark:/67375/WNG-6SLV811W-5 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23
ISSN:	0091-2700 1552-4604 1552-4604
DOI:	10.1002/jcph.392