The response to warfarin varies greatly among individuals. Some of this variability can be ascribed to genetic polymorphisms in the gene encoding for CYP2C9, the enzyme mediating the metabolism of S warfarin. In addition genetic polymorphism in other genes (i.e. VKORC1, factor VII) have been shown to account for some of the variability in the response to warfarin irrespective of CYP2C9.The present study has several segments: 1. Evaluation of the relationship between genetic polymorphisms in the genes encoding for CYP2C9, VKORC1 and factor VII and warfarin maintenance dose at steady state. This study is a confirmation of previous data in our own population. 2. Evaluation of relationship between genetic polymorphisms in the genes encoding for CYP2C9, VKORC1 and factor VII and warfarin loading dose during the induction period. 3. Testing the hypothesis that warfarin loading based on the individual's combined CYP2C9, VKORC1 and factor VII genotype may be more efficient and associated with reduced adverse drug effects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
500
Hadassah Medical Organization
Jerusalem, Israel
RECRUITINGPharmacokinetic end points:
Time frame: 1-4 months
Warfarin clearance and formation clearance of 7-hydroxy-warfarin at steady state
Time frame: 1-4 months
Pharmacodynamic.
Time frame: 1-4 months
Maintenance dose of warfarin at steady state.
Time frame: 1-4 months
Time to reach INR > 2.
Time frame: 1-4 months
Time to reach pharmacodynamic steady state.
Time frame: 1-4 months
Time spent at therapeutic INR <3 and >2.
Time frame: 1-4 months
Time spent at INR >3.
Time frame: 1-4 months
Time spent at INR <2.
Time frame: 1-4 months
The incidence of minor and major bleeding episodes.
Time frame: 1-4 months
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