How does VKORC1 affect warfarin?
Warfarin exerts its anticoagulant effect by inhibiting the enzyme encoded by VKORC1, which catalyzes the conversion of vitamin K epoxide to the active reduced form of vitamin K, vitamin K hydroquinone.
Is warfarin affected by CYP polymorphism?
It has been demonstrated that carriers of polymorphic alleles require significantly lower doses of warfarin than carriers of two wild-type alleles. Patients with polymorphic CYP2C9 alleles were reported to be more susceptible to bleeding complications.
What is CYP2C9 warfarin?
CYP2C9 is the primary enzyme responsible for inactivating warfarin. The CYP2C9*3 variant allele has been shown to cause an 80% decrease in enzymatic activity of CYP2C9 and therefore contributes to the dose variance of warfarin [4.
What drugs are metabolized by VKORC1?
3.2 VKORC1. Vitamin K epoxide reductase complex subunit 1, encoded by VKORC1 (chromosome 16), the drug target for the anticoagulants warfarin and acenocoumarol is used to prevent and treat thromboembolic cases. These drugs are metabolized primarily by the enzyme CYP2C9.
What does VKORC1 stand for?
vitamin K epoxide reductase complex subunit 1.
How is warfarin metabolized?
R-warfarin is metabolized primarily by CYP1A2 to 6- and 8-hydroxywarfarin, by CYP3A4 to 10-hydroxywarfarin, and by carbonyl reductases to diastereoisomeric alcohols. S-warfarin is metabolized primarily by CYP2C9 to 7-hydroxywarfarin.
Does warfarin inhibit CYP2C9?
Although R-warfarin is not metabolized by CYP2C9, this enantiomer binds and inhibits the enzyme with a Ki of ∼8 μM (13, 14). Furthermore, warfarin alcohols are known to competitively inhibit CYP2C9 yet are not metabolized (15).
What is CYP2C9 polymorphism?
CYP2C9 is highly polymorphic, with a total of 61 alleles reported, all of which have either reduced or no enzymatic activity. 21. A patient’s phenotype is calculated based on the genotype of the CYP2C9 allele, its heterozygosity or homozygosity (also referred to as diplotype).
What is VKORC1 gene?
The VKORC1 gene provides instructions for making a vitamin K epoxide reductase enzyme. The VKORC1 enzyme is made primarily in the liver. It spans the membrane of a cellular structure called the endoplasmic reticulum, which is involved with protein processing and transport.
What is low warfarin sensitivity?
Collapse Section. Warfarin sensitivity is a condition in which individuals have a low tolerance for the drug warfarin. Warfarin is an anticoagulant, which means that it thins the blood, preventing blood clots from forming.