Determination of plasma warfarin concentrations in Korean patients and its potential for clinical application.
BACKGROUND
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.
Kwon
Min-Jung
MJ
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kim
Hee-Jin
HJ
Kim
Jong-Won
JW
Lee
Kyung-Hoon
KH
Sohn
Kie-Ho
KH
Cho
Hyun-Jung
HJ
On
Young-Keun
YK
Kim
June-Soo
JS
Lee
Soo-Youn
SY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000097:blood* / Q000627:therapeutic use; D044466:Asian People; D001281:Atrial Fibrillation / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D056910:Republic of Korea; D053719:Tandem Mass Spectrometry; D014859:Warfarin / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use
D000925:Anticoagulants; D014859:Warfarin; C087837:7-hydroxywarfarin