Development of a pharmacogenetic-based warfarin dosing algorithm and its performance in Brazilian patients: highlighting the importance of population-specific calibration
Paulo Caleb Junior Lima Santos, Leiliane Rodrigues Marcatto, Nubia Esteban Duarte, Renata Alonso Gadi Soares, Celia Maria Cassaro Strunz, Maurício Scanavacca, Jose Eduardo Krieger, Alexandre Costa Pereira, Paulo Caleb Junior Lima Santos, Leiliane Rodrigues Marcatto, Nubia Esteban Duarte, Renata Alonso Gadi Soares, Celia Maria Cassaro Strunz, Maurício Scanavacca, Jose Eduardo Krieger, Alexandre Costa Pereira
Abstract
Background: The main aims of the present study were to develop a pharmacogenetic-based warfarin dosing algorithm and to validate it in a highly admixed population.
Materials & methods: We included two patient cohorts treated with warfarin (first cohort, n = 832; and second cohort, n = 133).
Results: Our algorithm achieved a determination coefficient of 40% including the variables age, gender, weight, height, self-declared race, amiodarone use, enzyme inducers use, VKORC1 genotypes and predicted phenotypes according to CYP2C9 polymorphisms.
Conclusion: Data suggest that our developed algorithm is more accurate than the IWPC algorithm when the application is focused on patients from the Brazilian population. Population-specific derivation and/or calibration of warfarin dosing algorithms may lead to improved performance compared with general use dosing algorithms currently available. Original submitted 26 November 2014; Revision submitted 9 April 2015.
Keywords: CYP2C9; VKORC; algorithm; warfarin.
Source: PubMed