p450 - publications

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1. Thromb Haemost. 2012 Apr 26;107(6). [Epub ahead of print]

A new algorithm to predict warfarin dose from polymorphisms of CYP4F2, CYP2C9 and
VKORC1 and clinical variables: Derivation in Han Chinese patients with non
valvular atrial fibrillation.

Wei M, Ye F, Xie D, Zhu Y, Zhu J, Tao Y, Yu F.

Junrong Zhu, Pharm D or Yifu Tao, Pharm D, Department of Clinical Pharmacology,
Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing,
Jiangsu 210006, China, Tel.: +86 025 52276287, Fax: +86 025 86620654, E-mail:
junrong_zhu@yahoo.com.cn or zjrtyf@yahoo.com.cn or Prof. Feng Yu, Department of
Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing,
Jiangsu 210009, China, Tel.: +86 025 83271262, E-mail: yufengcpu@163.com.

Few pharmacogenomic dosing regimens of warfarin have been developed for Chinese
patients with non valvular atrial fibrillation (NVAF). The objective of this
study was to develop a new algorithm by polymorphisms of CYP2C9 , VKORC1 and
CYP4F2 to predict daily stable dose of warfarin in Chinese patients with NVAF. A
total of 325 Chinese NVAF patients on stable dose of warfarin with a target
international normalised ratio of 1.5 to 3.0 were recruited and divided randomly
into two cohorts. CYP2C9 *3, VKORC1 -1639, VKORC1 1173 and CYP4F2 were detected
by ligase detection reaction method. The new algorithm was developed with
multivariate linear regression in cohort 1 (260 patients) and assessed with
Pearson Correlation Analysis (PCA) in cohort 2 (65 patients). From 260 enrolled
patients, the model (R2 = 51.7%) was developed as: Dose = 3.47 - 0.022 (AGE) +
0.017 (WT) + 0.189 (PTE) - 0.283 (β-blocker) - 0.471 (AMIO) - 0.586 ( CYP2C9
*1/*3) - 0.296 ( VKORC1 CT) - 0.648 ( VKORC1 TT) + 0.219 ( CYP4F2 TT). PCA
displayed that the algorithm was good (r = 0.658). The residual plots revealed
that predicted dose by the algorithm tend to be overestimated when lower doses
were administered to patients and be underestimated in higher doses. The
algorithm developed by us might predict warfarin dose used by Chinese NVAF
patients.

PMID: 22534826 [PubMed - as supplied by publisher]