Pharmacogenomics · 2016
A novel acenocoumarol pharmacogenomic dosing algorithm for the Greek population of EU-PACT trial.
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Ragia Georgia, Kolovou Vana, Kolovou Genovefa, Konstantinides Stavros, Maltezos Efstratios, Tavridou Anna, Tziakas Dimitrios, Maitland-van der Zee Anke H, Manolopoulos Vangelis G
Аннотация
AIM: To generate and validate a pharmacogenomic-guided (PG) dosing algorithm for acenocoumarol in the Greek population. To compare its performance with other PG algorithms developed for the Greek population.
PATIENTS & METHODS: A total of 140 Greek patients participants of the EU-PACT trial for acenocoumarol, a randomized clinical trial that prospectively compared the effect of a PG dosing algorithm with a clinical dosing algorithm on the percentage of time within INR therapeutic range, who reached acenocoumarol stable dose were included in the study.
RESULTS: CYP2C9 and VKORC1 genotypes, age and weight affected acenocoumarol dose and predicted 53.9% of its variability. EU-PACT PG algorithm overestimated acenocoumarol dose across all different CYP2C9/VKORC1 functional phenotype bins (predicted dose vs stable dose in normal responders 2.31 vs 2.00 mg/day, p = 0.028, in sensitive responders 1.72 vs 1.50 mg/day, p = 0.003, in highly sensitive responders 1.39 vs 1.00 mg/day, p = 0.029). The PG algorithm previously developed for the Greek population overestimated the dose in normal responders (2.51 vs 2.00 mg/day, p < 0.001).
CONCLUSION: Ethnic-specific dosing algorithm is suggested for better prediction of acenocoumarol dosage requirements in patients of Greek origin.
PATIENTS & METHODS: A total of 140 Greek patients participants of the EU-PACT trial for acenocoumarol, a randomized clinical trial that prospectively compared the effect of a PG dosing algorithm with a clinical dosing algorithm on the percentage of time within INR therapeutic range, who reached acenocoumarol stable dose were included in the study.
RESULTS: CYP2C9 and VKORC1 genotypes, age and weight affected acenocoumarol dose and predicted 53.9% of its variability. EU-PACT PG algorithm overestimated acenocoumarol dose across all different CYP2C9/VKORC1 functional phenotype bins (predicted dose vs stable dose in normal responders 2.31 vs 2.00 mg/day, p = 0.028, in sensitive responders 1.72 vs 1.50 mg/day, p = 0.003, in highly sensitive responders 1.39 vs 1.00 mg/day, p = 0.029). The PG algorithm previously developed for the Greek population overestimated the dose in normal responders (2.51 vs 2.00 mg/day, p < 0.001).
CONCLUSION: Ethnic-specific dosing algorithm is suggested for better prediction of acenocoumarol dosage requirements in patients of Greek origin.