Determination of Plasma Warfarin Concentrations in Korean Patients and Its Potential for Clinical Application

Abstract

, 건양대학교 의과대학 진단검사의학교실 5 515 515Background : Warfarin is a widely used oral anticoagulant with broad within-and between-individual dose requirements. Warfarin concentrations can be monitored by assessing its pharmacologic effects on International Normalized Ratio (INR). However, this approach has not been applied in the routine clinical management of patients receiving warfarin therapy. We performed a plasma warfarin assay using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) to determine if such an assay can be utilized in routine clinical practice.Methods : We included a total of 105 patients with atrial fibrillation, and who were receiving warfarin for more than 1 yr. The plasma concentrations of total warfarin and 7-hydroxywarfarin were determined by HPLC-MS/MS (Waters, UK). We assessed the association between warfarin dose, concentration, and INR as well as the effects of these factors on warfarin concentrations.Results : The mean maintenance dose of warfarin in 105 patients was 4.1±1.3 mg/day (range, 1.7-8.0 mg/day) and their mean plasma warfarin concentration was 1.3±0.5 mg/L. We defined a concentration range of 0.6-2.6 mg/L (corresponding to the 2.5th to 97.5th percentile range of the Plasma warfarin levels in the 74 patients showing INR within target range) as the therapeutic range for warfarin. The correlation of warfarin dose with warfarin concentration (r 2 =0.259, P<0.001) was higher than that with INR (r 2 =0.029, P=0.072). Conclusions : There was a significant correlation between warfarin dose and plasma warfarin concentrations in Korean patients with atrial fibrillation. Hence, plasma warfarin monitoring can help determine dose adjustments and improve our understanding of individual patient response to warfarin treatment. (Korean J Lab Med 2009;29:515-23)

Novel multi-mode ultra performance liquid chromatography–tandem mass spectrometry assay for profiling enantiomeric hydroxywarfarins and warfarin in human plasma

“…The presented method marks a significant advancement in the profiling of chiral warfarin and its hydroxylated metabolites. Prior studies have been limited to analyzing either warfarin enantiomers [23] or racemic forms of hydroxywarfarin metabolites [24,25]. Through the novel dual phase UPLC method, it is now possible to effectively assess the widest array of warfarin metabolites for identifying and validating potential biomarkers to metabolic pathways and surrogate markers corresponding to patient responses to warfarin therapy.…”

Anticoagulation of a patient with hypertrophic cardiomyopathy and factor VII deficiency

“…The plasma warfarin levels can also be measured although again there is very weak correlation between the two [11]. Some groups have suggested a therapeutic range of plasma warfarin level of 0.6-2.6 mg/l [11].…”

Development and validation of an ultra‐high‐performance liquid chromatography–tandem mass spectrometry method to determine the bioavailability of warfarin and its major metabolite 7‐hydroxy warfarin in rats dosed with oral formulations containing different polymorphic forms

“…Paralleling the use of new analytical methods is the application of a variety of sample preparation methods. Warfarin has been isolated from plasma matrices by solid‐phase extraction (Hou et al, ; Zuo et al, ), liquid/liquid extraction (Jones et al, ; Khvostov et al, ; Radwan, Bawazeer, Aloudah, AlQuadeib, & Aboul‐Enein, ) or simple protein precipitation (Kwon et al, ). Dried plasma spots were attempted by Chernonosov and co‐workers (Chernonosov, ) to quantify warfarin using HPLC–MS/MS.…”