A novel acenocoumarol pharmacogenomic dosing algorithm for the Greek population of EU-PACT trial

• Published in: Pharmacogenomics Vol. 18; no. 1; pp. 23 - 34
• Main Authors: Ragia, Georgia, Kolovou, Vana, Kolovou, Genovefa, Konstantinides, Stavros, Maltezos, Efstratios, Tavridou, Anna, Tziakas, Dimitrios, Maitland-van der Zee, Anke H, Manolopoulos, Vangelis G
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.01.2017
• Subjects: acenocoumarol; Acenocoumarol - administration & dosage; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Anticoagulants - administration & dosage; Clinical trials; CYP2C9; Diet; Dosage; Dose-Response Relationship, Drug; dosing algorithm; Drug dosages; Enzymes; Ethnicity; EU-PACT; European Union; Female; Follow-Up Studies; Genomics; Genotype & phenotype; Genotypes; Greece; Greece - ethnology; Humans; Male; Olive oil; Patients; Pharmacogenetics - methods; Pharmacogenomics; Phenotypes; Population; Population Surveillance - methods; Prospective Studies; Single-Blind Method; Vitamin K - antagonists & inhibitors; VKORC1; Greece; Netherlands; Greece; VKORC1; CYP2C9; pharmacogenomics; EU-PACT; acenocoumarol; dosing algorithm
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/pgs-2016-0126

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. 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. and 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). Ethnic-specific dosing algorithm is suggested for better prediction of acenocoumarol dosage requirements in patients of Greek origin.