The daily dose of warfarin varies widely in Asians due to variations in its metabolism between the difference ethnic groups. Tham et al derived a model that can predict the warfarin dose based on genotypic analysis of the patient. The authors are from National University Hospital (Singapore), Oncology Research Institute (Singapore) and Ordway Research Institute (Albany, New York).
Variations in warfarin metabolic enzymes
|
Enzyme |
Type |
Warfarin Dose |
|
vitamin K reductase |
VKORC1 381 H1H1 |
low dose |
|
|
VKORC1 381 H1H7 |
|
|
|
VKORC1 381 H1H* |
|
|
|
VKORC1 381 H7H7 |
|
|
|
VKORC1 381 H7H* |
high dose |
|
vitamin K reductase |
VKORC1 381 CC |
low dose |
|
|
VKORC1 381 TC |
|
|
|
VKORC1 381 TT |
|
|
CYP2C9 |
CYP2C9*1 |
|
|
|
CYP2C9*2 |
|
|
|
CYP2C9*3 |
low dose |
Racial variations:
(1) Chinese often require low dose therapy because of the H1H1 genotype.
(2) Indians often require higher doses because of the H7H7 genotype
(3) Malays show variable dosing requirements depending on genotype.
Parameters:
(1) age in years
(2) weight in kilograms
(3) presence of CYP2C9*3
(4) presence of vitamin K reductase VKORC1 381 CC
(5) presence of VKORC1 381 TC
|
Parameter |
Finding |
Points |
|
CYP2C9*3 |
absent |
0 |
|
|
present |
1 |
|
VKORC1 381 CC |
absent |
0 |
|
|
present |
1 |
|
VKORC1 381 TC |
absent |
0 |
|
|
present |
1 |
X =
= 0.838 – (0.005 * (age in years)) + (0.003 * (weight in kilograms)) – (0.189 * (points for CYP2C9*3)) – (0.0283 * (points for VKORC1 381 CC)) – (0.119 * (points for VKORC1 381 TC))
estimated daily warfarin dose requirement in mg =
= 10 ^(X)
where:
• Using 10 * EXP(X) results in absurdly high values.
Specialty: Hematology Oncology, Clinical Laboratory, Pharmacology, clinical
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