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Influence of CYP2C9 and VKORC1 polymorphisms on the time required to reach the therapeutic INR

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Author(s): Florentina C. Militaru | Sorin Crişan | Ştefan C. Vesa | Adrian Trifa | Valentin Militaru | Anca D. Buzoianu

Journal: Human & Veterinary Medicine
ISSN 2066-7655

Volume: 4;
Issue: 3;
Start page: 110;
Date: 2012;
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Keywords: oral anticoagulation | CYP2C9*2 | CYP2C9*3 | VKORC1 | therapeutic INR.

ABSTRACT
Oral anticoagulation (OAC) is characterized by a narrow therapeutic index and a high interindividual variability, both in terms ofpharmacokinetics and pharmacodynamics. We have considered useful and interesting to research the factors that could play a role in determiningthe time required for Acenocoumarol to achieve its optimal therapeutic response. Material and method: The present research is a cross analyticobservational study. We included 105 patients treated with an initial dose of 4 mg Acenocoumarol, for one or more of the following clinicalsituations: 1. Deep venous thrombosis of the lower limbs (DVT) ± pulmonary thromboembolism (PTE); 2. Permanent atrial fibrillation (AF);3. Prosthetic heart valve. Results and conclusions: The presence of CYP2C9*2 and CYP2C9*3 alleles did not affect the time required to reacha therapeutic INR. The c.-1639G>A polymorphism of the VKORC1 gene significantly and statistically influenced the time to reach the targetINR. The existence of a supratherapeutic INR during the initial phase of anticoagulant treatment causes a 35% lower probability of reaching atherapeutic INR on the fifth day of anticoagulant treatment.
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