Warfarin polymorphism effect

CYP2C19 Effects of CYP2C19 polymorphisms on the metabolism of warfarin are not yet elucidated, although this enzyme is known to metabolize warfarin (85)... 

D Andrea G, D Ambrosio RL, Di Perna P et al. A polymorphism in the VKORKCI gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood 2005 105 645-649. 

Dickinson et al. [38, 39] recently used (5)-warfarin and dextromethorphan as examples to demonstrate the value of incorporating mechanistic IVIVE models into population PK-PD models. Based on in vitro drug metabolism data and information on the frequency and activity of the different allelic forms of relevant CYPs, the statistical power of in vivo studies needed to discern the effect of genotypes on PK and PD was estimated. This approach represents a paradigm for assessing the impact of genetic polymorphisms on the PK and PD of new drugs prior to costly... 

Tabrizi, A.R. et al. The frequency and effects of cytochrome P450 (CYP) 2C9 polymorphisms in patients receiving warfarin. JAm Coll Surg 2002,194 267-273. 

An illustration of the effects of decreased CYP2C9 activity on a therapeutic compound is the effect on anticoagulation therapy with S-warfarin. Individuals with the CYP2C9 2 and CYP2C9 3 polymorphisms have impaired metabolism of warfarin and thus increased plasma concen-... 

Though not described in the text, genetic polymorphisms occur in isoforms of cytochrome P450. Variants in the CYP2D6 isoform have been implicated in excessive responses to codeine and nortriptyline, and variants in CYP2C9 may be responsible for unusual sensitivity to the anticoagulant effects of warfarin. 

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