Simplified Warfarin Dose-response Pharmacodynamic Models.
Warfarin is a frequently used oral anticoagulant for long-term prevention and treatment of thromboembolic events. Due to its narrow therapeutic range and large inter-individual dose-response variability, it is highly desirable to personalize warfarin dosing. However, the complexity of the conventional kinetic-pharmacodynamic (K-PD) models hampers the development of the personalized dose management. To avert this challenge, we propose simplified PD models for warfarin dose-response relationship, which is motivated by ideas from control theory. The simplified models were further applied to longitudinal data of 37 patients undergoing anticoagulation treatment using the standard two-stage approach and then compared with the conventional K-PD models. Data analysis shows that all models have a similar predictive ability, but the simplified models are most parsimonious.
Biostatistics Core, Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, MI.
Seongho
S
Kim
Department of Medicine, University of Louisville, Louisville, KY.
Adam E
AE
Gaweda
Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY.
Dongfeng
D
Wu
Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN.
Lang
L
Li
Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY.
Shesh N
SN
Rai
Department of Medicine, University of Louisville, Louisville, KY ; Robley Rex Veterans Medical Center, Louisville, KY.
Michael E
ME
Brier
dose-response model; kinetic-pharmacodynamics; mixed-effects model; standard two-stage approach