Development of a pharmacogenetic-guided warfarin dosing algorithm for Puerto Rican patients

被引:1
|
作者
Ramos, Alga S. [1 ]
Seip, Richard L. [2 ]
Rivera-Miranda, Giselle [3 ]
Felici-Giovanini, Marcos E. [4 ]
Garcia-Berdecia, Rafael [1 ]
Alejandro-Cowan, Yirelia [1 ]
Kocherla, Mohan [6 ]
Cruz, Iadelisse [1 ]
Feliu, Juan F. [3 ]
Cadilla, Carmed L. [7 ]
Renta, Jessica Y. [7 ]
Gorowski, Krystyna [6 ]
Vergara, Cunegundo [5 ]
Ruano, Gualberto [2 ]
Duconge, Jorge [1 ]
机构
[1] Univ Puerto Rico, Sch Pharm, Dept Pharmaceut Sci, San Juan, PR 00936 USA
[2] Hartford Hosp, Genet Res Ctr, Hartford, CT 06106 USA
[3] Veteran Affair Caribbean Healthcare Syst VACHS, San Juan, PR 00921 USA
[4] Puerto Rico Dept Hlth, Div Tobacco Control & Oral Hlth, San Juan, PR 00936 USA
[5] Hartford Hosp, Brownstone Outpatient Clin, Hartford, CT 06106 USA
[6] Genomas Inc, Hartford, CT 06106 USA
[7] Univ Puerto Rico, Sch Med, Dept Biochem, San Juan, PR 00936 USA
关键词
algorithm; CYP2C9; genotyping; personalized medicine; pharmacogenetics; VKORC1; warfarin; DOSE REQUIREMENTS; COMBINATORIAL CYP2C9; COAGULATION-FACTOR; ETHNIC-DIFFERENCES; AFRICAN-AMERICANS; VKORC1; GENOTYPES; POLYMORPHISMS; ASSOCIATION; GENE; ANTICOAGULATION;
D O I
10.2217/PGS.12.171
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aim: This study was aimed at developing a pharmacogenetic-driven warfarin-dosing algorithm in 163 admixed Puerto Rican patients on stable warfarin therapy. Patients & methods: A multiple linear-regression analysis was performed using log-transformed effective warfarin dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other relevant nongenetic clinical and demographic factors as independent predictors. Results: The model explained more than two-thirds of the observed variance in the warfarin dose among Puerto Ricans, and also produced significantly better 'ideal dose' estimates than two pharmacogenetic models and clinical algorithms published previously, with the greatest benefit seen in patients ultimately requiring <7 mg/day. We also assessed the clinical validity of the model using an independent validation cohort of 55 Puerto Rican patients from Hartford, CT, USA (R-2 = 51%). Conclusion: Our findings provide the basis for planning prospective pharmacogenetic studies to demonstrate the clinical utility of genotyping warfarin-treated Puerto Rican patients.
引用
收藏
页码:1937 / 1950
页数:14
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