title: Pharmacogenetic-guided Warfarin Dosing Algorithm in African-Americans.
abstract: We aim to develop warfarin dosing algorithm for African-Americans. We explored demographic, clinical, and genetic data from a previously collected cohort of 163 African-American patients with a stable warfarin dose. We explored 2 approaches to develop the algorithm: multiple linear regression and artificial neural network (ANN). The clinical significance of the 2 dosing algorithms was evaluated by calculating the percentage of patients whose predicted dose of warfarin was within 20% of the actual dose. Linear regression model and ANN model predicted the ideal dose in 52% and 48% of the patients, respectively. The mean absolute error using linear regression model was estimated to be 10.8 mg compared with 10.9 mg using ANN. Linear regression and ANN models identified several predictors of warfarin dose including age, weight, CYP2C9 genotype *1/*1, VKORC1 genotype, rs12777823 genotype, rs2108622 genotype, congestive heart failure, and amiodarone use. In conclusion, we developed a warfarin dosing algorithm for African-Americans. The proposed dosing algorithm has the potential to recommend warfarin doses that are close to the appropriate doses. The use of more sophisticated ANN approach did not result in improved predictive performance of the dosing algorithm except for patients of a dose of ≥49 mg/wk.
authors.affiliation: Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan.
authors.forename: Sameh
authors.initials: S
authors.lastname: Alzubiedi
authors.forename: Mohammad I
authors.initials: MI
authors.lastname: Saleh
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000465:Algorithms; D015331:Cohort Studies; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9