Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes

M. S. Wen; M. T.M. Lee; J. J. Chen; H. P. Chuang; L. S. Lu; C. H. Chen; T. H. Lee; C. T. Kuo; F. M. Sun; Y. J. Chang; P. L. Kuan; Y. F. Chen; M. J. Charng; C. Y. Ray; J. Y. Wu; Y. T. Chen

doi:10.1038/sj.clpt.6100453

Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes

M. S. Wen, M. T.M. Lee, J. J. Chen, H. P. Chuang, L. S. Lu, C. H. Chen, T. H. Lee, C. T. Kuo, F. M. Sun, Y. J. Chang, P. L. Kuan, Y. F. Chen, M. J. Charng, C. Y. Ray, J. Y. Wu, Y. T. Chen^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

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Abstract

Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements and could be used to predict warfarin dose. We conducted a prospective study in which warfarin dose was prescribed based on CYP2C9 and VKORC1 polymorphisms in 108 Han-Chinese patients without prior warfarin treatments. Using the genotype-based dosing, 83% of patients reached stable, therapeutic international normalized ratio (INR) within 2 weeks of treatment initiation and none of the patients developed clinical bleeding or thromboembolic event. Ten percent (11) of patients with INR >4 and no clinical bleeding were detected during this study. At 12 weeks, 69% of the patients' maintenance doses matched the prediction. Dosing algorithms incorporating genetic factors, age, and body surface area were developed, which could explain up to 62% of the total variation (R² of 0.62). This study demonstrated that pharmacogenetics-based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity.

Original language	English
Pages (from-to)	83-89
Number of pages	7
Journal	Clinical Pharmacology and Therapeutics
Volume	84
Issue number	1
DOIs	https://doi.org/10.1038/sj.clpt.6100453
State	Published - 07 2008

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Wen, M. S., Lee, M. T. M., Chen, J. J., Chuang, H. P., Lu, L. S., Chen, C. H., Lee, T. H., Kuo, C. T., Sun, F. M., Chang, Y. J., Kuan, P. L., Chen, Y. F., Charng, M. J., Ray, C. Y., Wu, J. Y., & Chen, Y. T. (2008). Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes. Clinical Pharmacology and Therapeutics, 84(1), 83-89. https://doi.org/10.1038/sj.clpt.6100453

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title = "Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes",

abstract = "Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements and could be used to predict warfarin dose. We conducted a prospective study in which warfarin dose was prescribed based on CYP2C9 and VKORC1 polymorphisms in 108 Han-Chinese patients without prior warfarin treatments. Using the genotype-based dosing, 83% of patients reached stable, therapeutic international normalized ratio (INR) within 2 weeks of treatment initiation and none of the patients developed clinical bleeding or thromboembolic event. Ten percent (11) of patients with INR >4 and no clinical bleeding were detected during this study. At 12 weeks, 69% of the patients' maintenance doses matched the prediction. Dosing algorithms incorporating genetic factors, age, and body surface area were developed, which could explain up to 62% of the total variation (R2 of 0.62). This study demonstrated that pharmacogenetics-based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity.",

author = "Wen, {M. S.} and Lee, {M. T.M.} and Chen, {J. J.} and Chuang, {H. P.} and Lu, {L. S.} and Chen, {C. H.} and Lee, {T. H.} and Kuo, {C. T.} and Sun, {F. M.} and Chang, {Y. J.} and Kuan, {P. L.} and Chen, {Y. F.} and Charng, {M. J.} and Ray, {C. Y.} and Wu, {J. Y.} and Chen, {Y. T.}",

year = "2008",

month = jul,

doi = "10.1038/sj.clpt.6100453",

language = "英语",

volume = "84",

pages = "83--89",

journal = "Clinical Pharmacology and Therapeutics",

issn = "0009-9236",

publisher = "Wiley-Blackwell",

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AU - Wen, M. S.

AU - Lee, M. T.M.

AU - Chen, J. J.

AU - Chuang, H. P.

AU - Lu, L. S.

AU - Chen, C. H.

AU - Lee, T. H.

AU - Kuo, C. T.

AU - Sun, F. M.

AU - Chang, Y. J.

AU - Kuan, P. L.

AU - Chen, Y. F.

AU - Charng, M. J.

AU - Ray, C. Y.

AU - Wu, J. Y.

AU - Chen, Y. T.

PY - 2008/7

Y1 - 2008/7

N2 - Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements and could be used to predict warfarin dose. We conducted a prospective study in which warfarin dose was prescribed based on CYP2C9 and VKORC1 polymorphisms in 108 Han-Chinese patients without prior warfarin treatments. Using the genotype-based dosing, 83% of patients reached stable, therapeutic international normalized ratio (INR) within 2 weeks of treatment initiation and none of the patients developed clinical bleeding or thromboembolic event. Ten percent (11) of patients with INR >4 and no clinical bleeding were detected during this study. At 12 weeks, 69% of the patients' maintenance doses matched the prediction. Dosing algorithms incorporating genetic factors, age, and body surface area were developed, which could explain up to 62% of the total variation (R2 of 0.62). This study demonstrated that pharmacogenetics-based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity.

AB - Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements and could be used to predict warfarin dose. We conducted a prospective study in which warfarin dose was prescribed based on CYP2C9 and VKORC1 polymorphisms in 108 Han-Chinese patients without prior warfarin treatments. Using the genotype-based dosing, 83% of patients reached stable, therapeutic international normalized ratio (INR) within 2 weeks of treatment initiation and none of the patients developed clinical bleeding or thromboembolic event. Ten percent (11) of patients with INR >4 and no clinical bleeding were detected during this study. At 12 weeks, 69% of the patients' maintenance doses matched the prediction. Dosing algorithms incorporating genetic factors, age, and body surface area were developed, which could explain up to 62% of the total variation (R2 of 0.62). This study demonstrated that pharmacogenetics-based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity.

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JO - Clinical Pharmacology and Therapeutics

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Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes

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