Drug Metab. Pharmacokinet. 25 (6): 531–538 (2010).

Regular Article
Pharmacokinetic and Pharmacodynamic
Variation Associated with VKORC1 and
CYP2C9 Polymorphisms in Thai Patients Taking Warfarin
Alisara SANGVIROON1,2, Duangchit PANOMVANA1,*,
Wichittra TASSANEEYAKUL3 and Jule NAMCHAISIRI4

1 Departmentof Pharmacy Practice, Faculty of Pharmaceutical Sciences,

Chulalongkorn University, Bangkok, Thailand
2 Department of Pharmacy, Police General Hospital, Bangkok, Thailand
3Department of Pharmacology, Faculty of Medicine, Khon kaen University, Khon kaen, Thailand
4Cardiothoracic Unit, Department of Surgery, Faculty of Medicine Chulalongkorn University, Bangkok, Thailand

Full text of this paper is available at http://www.jstage.jst.go.jp/browse/dmpk

Summary: We investigated the influence of genetic polymorphisms of CYP2C9 and VKORC1 genotypes on
the pharmacokinetics and pharmacodynamics of warfarin and established an equation for predicting the
maintenance dose of warfarin in the Thai population using genetic and non-genetic factors. The CYP2C9*2,
CYP2C9*3, VKORC1 C1173T and VKORC1 G1639A genotypes were detected by realtime PCR using
fluorogenic hybridization probes. The associations between genetic and demographic factors with respect to
warfarin dosage were analyzed. CYP2C9 polymorphisms affect warfarin metabolism as shown by a significant
difference in warfarin clearance, whereas VKORC1 genotypes cause a significant difference in warfarin sen-
sitivity index (INR:Cp). The mean weekly warfarin dose was significantly different among different VKORC1
and CYP2C9 genotypes. Patients with the VKORC1 BB haplotype and CYP2C9*1/*1 required about twice
the warfarin dose compared to those with the VKORC1 AA haplotype and CYP2C9*1/*1. Using stepwise
multiple linear regression, clinical factors (age and weight) and genetic factors (CYP2C9 and VKORC1) could
explain about 53.8z of the variance of the warfarin maintenance dose. CYP2C9 and VKORC1 genotypes
played an important role in the inter-individual variation in warfarin maintenance dose in a Thai population.

Keywords: CYP2C9; VKORC1; Warfarin; Thai; Pharmacokinetics; Pharmacodynamics

and pharmacodynamic parameters of warfarin can be in-

Introduction
Warfarin, an oral anticoagulant, is metabolized to an
inactive form by cytochrome P450 (CYP) enzymes in the
liver. While S-isomer warfarin is oxidized by CYP2C9,
CYP2C19 and CYP2C18, the R-isomer is oxidized by
CYP1A1, CYP1A2 and CYP3A4.1) Warfarin exerts its an-
ticoagulant effect by inhibiting vitamin K epoxide reduc-
tase (VKOR), encoded by vitamin K epoxide reductase
complex subunit 1 (VKORC1), thus interrupting the con-
version of vitamin K epoxide to vitamin KH2, a cofactor
in the gamma-carboxylation process of activation of the
vitamin K-dependent proteins.2–4) The pharmacokinetic
fluenced by many factors and this fact makes it difficult
to adjust or predict the appropriate dose for individual
patients; the correct dose can depend on intra- and inter-
individual differences and ethnicity.
Recently, at least 30 alleles of CYP2C9 have been iden-
tified (http://www.imm.ki.se/CYPalleles). CYP2C9*2 and
CYP2C9*3 have reduced enzymatic activity by about 30%
and 80%, respectively.5,6) Single nucleotide polymor-
phisms in CYP2C9 are associated with a lower dose re-
quirement of warfarin during the induction phase and
maintenance phase.7–12) Lindh, et al.13) have shown a sys-
tematic review and meta-analysis of the influence of

Received; June 29, 2010, Accepted; July 28, 2010, J-STAGE Advance Published Date; October 1, 2010
*To whom correspondence should be addressed: Duangchit PANOMVANA, Ph.D. Department of Pharmacy Practice, Faculty of Pharmaceutical
Sciences, Chulalongkorn University, Bangkok, Thailand. Tel. ＋662-2188405, Fax. ＋662-2188403, E-mail: duangchit.p＠chula.ac.th
This study was supported by Chulalongkorn University, Bangkok, Thailand. The VKORC1 reagents were supported by Roche Diagnostic,
Thailand.

531
532 Alisara SANGVIROON, et al.
CYP2C9 genotype on warfarin dose requirement and
found that patients with CYP2C9*1/*2, *1/*3, *2/*2,
*2/*3, and *3/*3 genotypes required warfarin doses
about 19.6, 33.7, 36.0, 56.7, and 78.1% lower than
those with the CYP2C9*1/*1 genotype (wild type), respec-
tively.
It has been reported that VKORC1 is associated with an
interindividual variability in the dose of warfarin.14) As
Rieder, et al.15) have identified, VKORC1 haplotype group
A is consisted of H1 and H2 haplotypes which is associ-
ated with a low warfarin dose requirement and is com-
monly found in the Asian-American population. Haplo-
type group B comprises H7, H8 and H9 haplotypes and is
associated with a high warfarin dose requirement; this
group is common in African-Americans. In Asians, Yuan
et al.16) have shown that the G allele in the VKORC1
promoter (G-1639A) had 44% higher activity than the A
allele. Moreover, the frequencies of GG, GA and AA
were significantly different from those in Caucasians
(pº0.0001).
Several studies have investigated the association be-
tween warfarin doses and CYP2C9 and VKORC1 geno-
types in different populations. The contribution of clini-
cal factors and genetic factors to variability in the warfa-
rin requirement was reported to be about 30–60%.17–22)
However, a best-fit equation to predict warfarin dose re-
quirement for the Thai population has not yet been
proposed. In addition, the frequencies of CYP2C9 vari-
ants are different among various ethnic groups.
CYP2C9*2 is found in about 8–20% of Caucasians but is
not found in Asians (Japanese, Chinese, Taiwanese,
Korean, Malaysian and Singaporean); also, the frequen-
cies of CYP2C9*3 are higher in Caucasians (5–16%) than
in Asians (about 1–5%).23) Therefore, the purpose of this
study was to investigate the frequencies of CYP2C9 and
VKORC1 genotypes in a Thai population, to evaluate the
effect of CYP2C9 and VKORC1 genotypes on the phar-
macokinetic and pharmacodynamic parameters of warfa-
rin, and to establish an equation for prediction of the
maintenance dose of warfarin by using genetic and non-
genetic factors in the Thai population.
Methods
Patients: The subjects enrolled in this study were
outpatients at the cardiovascular thoracic unit, The King
Chulalongkorn Memorial Hospital, Bangkok, Thailand
who had taken warfarin for at least 2 months and had
taken a stable dose for at least the last 2 visits. Patients
who had congestive heart failure, cancer, hepatic or
thyroid disorders were excluded. The study protocol was
approved by The Ethics Committee of the Faculty of
Medicine, Chulalongkorn University, Bangkok, Thailand.
All patients gave informed consent to participate in the
study.
The patient data, including gender, age, weight, under-
lying diseases, dose of warfarin, co-medications, INR lev-
el, time of taking the last dose of warfarin and vitamin K-
containing food consumption (within the week before
INR testing), were collected.
Determination of warfarin concentrations: The
total concentrations of warfarin in plasma were deter-
mined by high-performance liquid chromatography
(HPLC), as previously described with some modifica-
tions.24) In brief, 1 ml of plasma sample was added to a
tube and 50 ml of internal standard (naproxen 100
mg/ml), 0.7 ml of 1 M sulfuric acid and 5 ml of diethyl
ether were then added. The mixture was briefly mixed by
vortex for 5 seconds and rotary mixed at 300 rpm for 30
minutes. The tubes were then centrifuged at 600 rpm for
10 minutes and kept in a freezer at －209C for 3 hours.
The diethyl ether layer was decanted from a frozen aque-
ous layer to a clean tube and then evaporated to dryness
in a heat box at 459C. The residue was dissolved in 250
mL of acetonitrile in water (25:75 v/v). A volume of 100
mL of the solution was injected into the chromatograph, a
HyperClone C18-BDS 5 mm, column 150×4.6 mm
(Phenomenex). The mobile phase consisted of 15 mM of
phosphate buffer (pH 3.0, adjusted by 1 M HCl),
methanol, acetonitrile (52:32:16 v/v). The flow rate was
1.2 ml/min. Validation of the HPLC method including
linearity, specificity, selectivity, precision, accuracy, and
stability were performed (data not shown).
gDNA preparation: Nine milliliters of whole blood
from a peripheral vein was drawn into an EDTA tube.
The genomic DNA was extracted by the standard phenol-
chloroform extraction protocol.
CYP2C9 and VKORC1 genotyping: The genotypes
of CYP2C9 and VKORC1 were determined by realtime
polymerase chain reaction using fluorogenic hybridiza-
tion probes (TIB MOLBIOL, Berlin, Germany), as previ-
ously described.25–27)
Data and statistical analysis: Since warfarin is a
long half-life drug taken once daily, the total warfarin
concentration in the plasma sample was assumed to be
the average steady state concentration (Cssav); the clear-
ance (Cl) was then calculated using the following formu-
la:
Cl＝Dose/Cssav* dosing interval
Descriptive statistics and inferential statistics were
performed using the SPSS program version 14. The
warfarin dose and prevalence of CYP2C9 and VKORC1
genotypes are shown as means and 95% confidence inter-
vals. The warfarin dose, clearance, warfarin sensitivity in-
dex between different CYP2C9 and VKORC1 genotypes
were compared by independent t-test, ANOVA, Mann-
Whitney U test or Kruskal-Wallis test. The association of
all factors to doses of warfarin were analyzed by forward
stepwise multiple linear regressions. The characteristic
factors analyzed included age, gender, weight, and co-
 VKORC1-CYP2C9 Variation on Warfarin Kinetic & Dynamic 533

Table 1. Demographic data Table 2. CYP2C9 and VKORC1 genotype frequencies in a Thai
population
Frequency,
Characteristics %, (range)
(mean±SD) (89 patients×2 alleles)
Total number (N) 89 Alleles N＝178 % [95%CI]

Female 48 53.9 CYP2C9 *1 173 97.2 [93.6–98.8]

*2 0 0 —
Age (years) (49.25±13.09) (21–78)
*3 5 2.8 [1.2–6.4]
Weight (kg) (57.10±10.62) (30–96)
VKORC1 C 40 22.5 [17.0–29.2]
2
BMI (kg/m ) (22.04±4.02) (13.67–36.21) 1173CÀT
Indications T 138 77.5 [70.9–83.0]
Mitral Valve Replacement 43 48.3 VKORC1 G 40 22.5 [17.0–29.2]
Aortic Valve Replacement 21 23.6 －1639GÀA
Double Valve Replacement 21 23.6 A 138 77.5 [70.9–83.0]
Others 4 4.5 r＝1.0***
Co-medications *** Significant at pº0.0001.
Lasix 34 47.9
HCTZ 13 18.3
Aspirin 9 12.7
Aldactone 6 8.4
Statins 4 5.6
Allopurinol 2 2.8
Omeprazole 2 2.8
Celebrex 1 1.4

INR (2.2±0.5) (1.5–3.5)

Warfarin dose (mg/day) (3.7±1.5) (0.64–10)

Warfarin dose (mg/kg/wk) (0.466±0.209) (0.062–1.591)

HCTZ, hydrochlorothiazide.

medication. A p-value of less than 0.05 was considered

statistically significant for all analyses.
Results
Eighty nine Thai patients with an established stable
warfarin maintenance dose who met the criteria were en-
rolled into this study. The major indication for taking
warfarin (95.5%) was prosthetic heart valve replacement.
Other indications were Bental's operation, pulmonary
embolism, PA thrombectomy, and commissurotomy.
Patient characteristics are summarizes in Table 1.
The CYP2C9 and VKORC1 genotypes of these patients
are shown in Table 2. The CYP2C9*2 genotype was not Fig. 1. Comparison of warfarin clearances among different
found in the studied population (0%). The allele fre- CYP2C9 (***pº0.0001) (a) and VKORC1 genotypes (no sig-
quency of CYP2C9*3 observed in these patients was nificant difference, p＝0.909) (b) (N＝89)
0.028 [95%CI 0.012–0.064]. The most common geno-
type in Thais was the wild type, CYP2C9*1/*1 (95.5%).
One patient had the CYP2C9*3/*3 genotype (1.1%) and 3 patients, 55 (61.8%) carried VKORC1 AA haplotypes
patients had CYP2C9*1/*3 (3.4%). The frequencies of (``low dose group'') whereas 28 patients (31.5%) had the
VKORC1 1173T and －1639A were both 0.775 [95%CI AB genotype and 6 patients (6.7%) had the VKORC1 BB
0.709–0.830], indicating that VKORC1 1173CÀT was haplotype. All allele frequencies were in Hardy-Weinberg
completely correlated with VKORC1 －1639GÀA (Pear- equilibrium.
son's correlation＝1.0, pº0.0001). Among these The mean total warfarin concentration in plasma of all
534 Alisara SANGVIROON, et al.

patients was 948.7±451.8 ng/ml (range, 238.8 to

2,488.1 ng/ml). Concomitant drugs were reported as not
interfering with the determination of warfarin concentra-
tion. Clearance (Cl) was 0.052±0.021 ml/min/kg (range
0.009–0.114 ml/min/kg). Figure 1 shows that warfarin
clearance was significantly lower in the variant group of
CYP2C9 polymorphisms (CYP2C9*1/*3 and *3/*3) as
compared to wild type (CYP2C9*1/*1) (pº0.0001).
However, clearances were not significantly different
among VKORC1 haplotypes (p＝0.909).
The ratio of INR:warfarin plasma concentration
(INR:Cp), which is defined as the warfarin sensitivity in-
dex (WSI), was analyzed as a pharmacodynamic
parameter. In this study, the total plasma warfarin con-
centration (a mixture of S- and R-warfarin) was used in-
stead of plasma S-warfarin concentration in the calcula-
tion of the INR:Cp ratio. Patients with a high INR:Cp ra-
tio need a lower dose of warfarin to control the INR in
range as compared to those with a low INR:Cp ratio.
Therefore, patients with a high WSI are more sensitive to
warfarin than those with low WSI. The effect of VKORC1
genotypes on WSI were compared among 85 patients
with the same CYP2C9 genotype (CYP2C9*1/*1) to
eliminate the effect of CYP2C9 polymorphism on WSI.
The WSI in the VKORC1 AA group was significantly great-
er than those in the VKORC1 BB & AB group, 3.02±1.08
and 2.05±0.95, respectively (pº0.0001). However, Fig. 2. Warfarin sensitivity index for different CYP2C9 geno-
WSI was not significantly different between types of the same VKORC1 AA genotype (N＝55, p＝0.213) (a)
CYP2C9*1/*1 and the CYP2C9*1/*3 & CYP2C9*3/*3 and different VKORC1 genotypes of the same CYP2C9 *1 /*1
genotype (N＝85, ***pº0.0001) (b).
group among the 55 patients with the same VKORC1 AA
haplotype, p＝0.213 (Fig. 2).
The mean warfarin doses among different CYP2C9 Table 3. Comparison of weekly warfarin doses between
genotypes were significantly different. The warfarin dose CYP2C9 genotypes
in the CYP2C9*3 group (0.229±0.195 mg/kg/wk) was
CYP2C9 N Warfarin dose
significantly lower than that in the wild type group genotypes (89) (mg/kg/wk)
INR
(0.477±0.204 mg/kg/wk), p＝0.020 [95%CI 0.041–
Wild type 85 0.477±0.204 2.1±0.5
0.455] (Table 3). The mean warfarin dose in the group
*1 /* 1
(95.5%)
VKORC1 high-dose group (BB) was 0.842±0.403
Variant 3 0.285±0.196 2.4±0.3
mg/kg/wk, in the AB group it was 0.550±0.148 group
*1 /*3
(3.4%)
mg/kg/wk, while in the low-dose group (AA) it was 0.381 *3 /*3 1 0.062 3.5
±0.135 mg/kg/wk (Table 4). There were significant (1.1%)
differences between warfarin maintenance doses among *1/*3 and *3/*3 4 0.229±0.195 2.7±0.6
different VKORC1 haplotype groups, pº0.0001. Patients (4.5%)
with the VKORC1 BB haplotype and CYP2C9*1/*1 re- Sig. p＝0.020* p＝0.026*
quired the highest warfarin maintenance dose, while the * Significant at pº0.05 between variant and wild type groups.
patient with the VKORC1 AA haplotype and CYP2C9*3/*3
required the lowest warfarin maintenance dose. Most of
this Thai population were VKORC1 AA haplotype,
CYP2C9*1/*1 and required only about 50% of the warfa- ence group and is shown (Fig. 3) as the percentage
rin dose required by the highest dose group (VKORC1 BB difference in warfarin dose. The warfarin doses for
haplotype, CYP2C9*1/*1) (Table 4). VKORC1 AA/CYP2C9*1/*3 and VKORC1 AA/CYP2C9*3/*3
A warfarin dose of 21 mg/wk (about 0.4 mg/kg/wk), were about 50% and 80% less than the reference dose,
which was the most common optimum dosage used, was respectively, but for VKORC1 BB/CYP2C9*1/*1, VKORC1
set as a reference line. The weekly warfarin dose of each AB/CYP2C9*1/*1 and VKORC1 AB/CYP2C9*1/*3, the
different genotype group was compared with this refer- doses of warfarin were about 120%, 40% and 30% higher
 VKORC1-CYP2C9 Variation on Warfarin Kinetic & Dynamic 535

Table 4. Comparisons of weekly warfarin doses among VKORC1 genotypes

VKORC1 CYP2C9 N Weekly warfarin dose Approximate % of

INR
(89) (mg/kg/wk) dose compare to ref.

BB * 1/*1 6 0.842±0.403 2.3±0.3 220%

(1173CC, －1639GG) * 1/*3 0 — —
* 3/*3 0 — —

6 0.842±0.403 2.3±0.3
Total
(6.7%)
AB * 1/*1 27 0.552±0.151 2.1±0.5 140%
(1173CT, －1639GA) * 1/*3 1 0.509 2.3 130%
* 3/*3 0 — —

28 0.550±0.148 2.1±0.5
Total
(31.5%)
AA * 1/*1 52 0.395±0.124 2.2±0.5 100% (Ref.)
(1173TT, －1639AA) * 1/*3 2 0.173±0.041 2.5±0.4 50%
* 3/*3 1 0.062 3.5 20%

55 0.381±0.135ab 2.2±0.5
Total
(61.8%)

Sig. pº0.0001*** p＝0.402

*** Significant at pº0.0001.
a
pº0.0001 between AB and AA groups.
b
pº0.0001 between BB and AA groups.

Table 5. Multivariate analysis: coefficients of factors in the

best fit equation for prediction of warfarin dose requirement
Weekly warfarin dose (mg/wk)＝exp [1.846＋(0.412×VKORC1 AB)＋(0.559
×VKORC1 BB)＋(1.512×CYP2C9*1/*1)＋(1.136×CYP2C9*1/*3)－(0.007×
age)]

Factors Coefficient SE p value

Constant 1.846 0.314 º0.0001

VKORC1 AB 0.412 0.068 º0.0001
VKORC1 BB 0.559 0.125 º0.0001
CYP2C9*1/*1 1.512 0.292 º0.0001
CYP2C9*1/*3 1.136 0.334 0.001
Age －0.007 0.002 0.007
Body weight (Kg) 0.149 nd 0.055

nd＝no data.

Fig. 3. Mean weekly warfarin dose requirement associated

with different genotypes as compared to standard dose
(warfarin 21 mg/week (0.4 mg/kg/wk) was use as the standard
dose). nd＝no data.
than the reference dose, respectively. Patients older than
65 years required a lower dose of warfarin to achieve the
optimum INR as compared to those patients who were
younger.
Using stepwise multiple linear regressions (Table 5),
age and genetic factors (CYP2C9 and VKORC1) could ex-
plain approximately 53.8% of the variance in warfarin
maintenance dose based on the following equation:
Weekly warfarin dose (mg/wk)＝exp [1.846＋(0.412
×VKORC1 AB)＋(0.559×VKORC1 BB)＋(1.512×
CYP2C9*1/*1)＋(1.136×CYP2C9*1/*3)－(0.007×age)].
Input the age in years and 1 or 0 if present or absent in
terms of CYP2C9*1/*1, CYP2C9*1/*3, VKORC1 AB or
VKORC1 BB. There was a highly significant correlation
between the observed warfarin dose and the predicted
dose using the aforementioned equation (r＝0.734,
pº0.0001) (Fig. 4).
In addition, this study compared the percentage of
patients whose predicted weekly warfarin doses were wi-
thin 15% of the observed dose for 3 different prediction
methods. The first method set the predicted dose to be a
536 Alisara SANGVIROON, et al.
Fig. 4. Scatter plot of observed warfarin dose versus predict-
ed warfarin dose from equation (log-transformed data)
Fig. 5. Bar charts show percentage of patients whose predict-
ed weekly warfarin doses were within 15% of the observed
doses
Fixed dose: 21 mg/week
Simple method: based on data from Figure 3
Equation method: based on equation from Table 5
fixed dose of warfarin equal to 21 mg/week. The second
method, called the simple method, predicted the dose
from the percentage difference in dosage requirement as-
sociated with different genotypes as shown in Figure 3.
The third method, called the equation method, predicted
the dose from the equation generated above. The equa-
tion method and the simple method could predict warfa-
rin dose better than the fixed-dose method (Fig. 5).
Discussions
In this study, we found that CYP2C9*3 and VKORC1 AA
groups were associated with a lower required dose of
warfarin. CYP2C9*3 was associated with lower clearance
of warfarin and, therefore, required a lower dose of
warfarin than the wild type group. In addition, the warfa-
rin sensitivity index (INR:Cp) in the VKORC1 AA group
was higher than those in VKORC1 BB and AB groups; thus,
VKORC1 AA group required a lower dose of warfarin. It
was demonstrated that warfarin clearance was not sig-
nificantly different among VKORC1 AA, AB and BB haplo-
types; this finding suggested that VKORC1 haplotypes had
no association with the pharmacokinetics of warfarin,
but they are likely to have some effect on the phar-
macodynamics of warfarin. VKORC1 AA patients were
more sensitive to the same concentration of warfarin as
compared to VKORC1 AB or BB patients.
In Asians, variations in VKORC1 haplotypes were
found more frequently than variations in CYP2C9 poly-
morphisms.21,28) The allele frequencies of CYP2C9 and
VKORC1 genotypes found in this study were not different
from those reported for a Northern Thai population.28) It
has been reported previously that variation in VKORC1 is
one of the factors causing variation in warfarin doses
among Asians.21,22,29,30) VKORC1 haplotype frequencies in
Thais were different from other Asians such as Chinese,
Japanese, Malaysian and Indian.21,28–31) Mushiroda, et al.30)
reported that VKORC1 BB, AB and AA groups in 828
Japanese patients were 0.8%, 15.9% and 83.3%, respec-
tively. The present study found that the frequency of
VKORC1 BB, AB and AA groups in Thai population was
6.7%, 31.5% and 61.8%, respectively. It was significantly
different from those of the Japanese (chi square＝35.34,
pº0.0001). Moreover, these were also significantly
different from the Chinese population, in which the
reported frequencies of VKORC1 BB, AB and AA groups
were 1.5%, 21.1% and 77.4%, respectively32) (chi square
＝11.77, p＝0.003).
Genetic factors played an important role in the inter-
individual variation in warfarin maintenance dose in a
Thai population. The warfarin dose depended about
31.4% on VKORC1 and about 22.5% on CYP2C9.
VKORC1 was associated with pharmacodynamic
parameters such as the warfarin sensitivity index
(INR:Cp). S-warfarin plasma concentration should be
used in the calculation of warfarin sensitivity index, not
the racemic mixture of S- and R-warfarin, to reflect
genuine warfarin sensitivity; however, due to the limita-
tion of the analytical instruments of this study, the total
warfarin concentration was determined. It should be not-
ed that the same brand of warfarin was used throughout
the study to ensure uniformity in the ratio of S- to R-
warfarin that each patient received. Therefore, the use of
WSI calculated from the total warfarin concentration
might be justified for comparison of the differences be-
tween genotypes.
CYP2C9 polymorphism was apparently associated with
the clearance of warfarin. The warfarin sensitivity index
appeared to be higher in the CYP2C9 variant group, but
 VKORC1-CYP2C9 Variation on Warfarin Kinetic & Dynamic
did not reach statistical significance because only a few
patients with variant CYP2C9 (n＝3) were enrolled in this
study comparison (Fig. 2a). A larger number of patients
with CYP2C9*1/*3 or *3/*3 is needed if a significant
difference in warfarin sensitivity index is to be detected.
This study also gives a stepwise multiple linear regres-
sion model for estimation of the warfarin maintenance
dose for Thai patients. Using simplified factors including
age, CYP2C9*3 and VKORC1 genotypes could explain
about 53.8% of the variance of warfarin maintenance
dose. A rapid genotyping method giving results within an
hour may increase the possibility of incorporating these
factors in setting the individual warfarin dose in clinical
practice.33) Recently, a prospective study has shown that
a pharmacogenetics-based dosing method could reach
the stable dose in a shorter time than the traditional
method (p＝0.001).32) However, future research with
prospective randomized controlled clinical studies are re-
quired to determine the cost-benefit outcome from a
genetic-based dosing regimen.
Acknowledgments: We are grateful to all patients who
took part in this study. Our thankfulness is extended to
Chulalongkorn University, Bangkok, Thailand for finan-
cial support. The VKORC1 reagents were supported by
Roche Diagnostic, Thailand.
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