Background: Warfarin has been widely used for a long time as an oral anticoagulant agent. Warfarin is reported to have inflammatory role as well. The dose of Warfarin plays an important role in up and down regulation of interacting cytokines such as IL-6 and COX-2 (Cyclooxygenase). Objective: To investigate the effects of varying Warfarin doses on IL-6 and COX-2. Material and Methods: Serum IL-...

Cytochrome P450 oxidoreductase (POR) is required for drug metabolism by all microsomal cytochrome P450 enzymes. The aim of this study was to investigate whether any of the common single nucleotide polymorphisms (SNPs) in the POR gene and its flanking intergenic sequences correlate with interindividual variations in the warfarin maintenance dose (which is determined partly by rates of warfarin m...

Warfarin induction is accomplished by titrating dosage to coagulation test results. Algorithms can guide this process but not identify the starting dose. We hypothesized that an initial warfarin dose approximating the maintenance value would safely enhance rapidity of induction. In a randomized trial we compared a fixed-dose to a maintenance-dose strategy for beginning warfarin therapy. To pred...

Variations in the rate of response to a given dose of warfarin have been problematic. Effective daily doses can range from as low as 0.5 mg to higher than 60 mg. In an effort to make sense of the puzzle, Aithal and colleagues conducted a case–control study to determine whether genetic differences in the cytochrome P450 system influence the individual variability in dose requirements for warfari...

The aim of this study was to determine the association of bleeding as a complication of warfarin therapy with polymorphism of CYP2C9 gene (alleles 1, 2 and 3). The CYP2C9 is the main enzyme for warfarin metabolism. Study included 181 patients receiving warfarin for at least one month. Allele 1 of CYP2C9 gene (in 94.5%) and genotype *1/*1 (57.5%) prevailed. Allele 3 was found in 12.7% patients. ...

Genetic variants in CYP2C9 and VKORC1 strongly affect steady-state warfarin dose. However, these variants also affect early international normalized ratio (INR) values during warfarin initiation. We examined whether CYP2C9/VKORC1 genotypes provide information about warfarin sensitivity additional to that provided by early INR responses. In 214 patients starting warfarin with INR-guided dose adj...

a case to illustrate the utility of genetic screening in warfarin (Coumadin®) management is reported. a 45 year-old woman of puerto rican ancestry was admitted to the emergency room twice within one month with chest pain. she was diagnosed with congestive heart failure, which was stabilized both times. at her second release, warfarin therapy was initiated at 5 mg/ day to prevent thrombus format...

Genetic variants in CYP2C9 and VKORC1 strongly affect steady-state warfarin dose. However, these variants also affect early international normalized ratio (INR) values during warfarin initiation. We examined whether CYP2C9/VKORC1 genotypes provide information about warfarin sensitivity additional to that provided by early INR responses. In 214 patients starting warfarin with INR-guided dose adj...

Laropiprant (LRPT), a prostaglandin D2 receptor 1 antagonist shown to reduce niacin-induced flushing symptoms, is being developed in combination with niacin for the treatment of dyslipidemia. This study assessed the pharmacokinetics/pharmacodynamics of single-dose warfarin in the presence/absence of multiple-dose LRPT. Thirteen subjects received 2 treatments in random order separated by > or =1...

BACKGROUND Warfarin is an anticoagulant and is widely used for the prevention of thromboembolic events. Genetic variants of the enzymes that metabolize warfarin, i.e. cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1), contribute to differences in patients' responses to various warfarin doses. There is, however, a dearth of data on the role of these variants during initial an...