Performance of a Theory-Based Mechanistic Model for Predicting the Target Dose of Warfarin

Background: Warfarin is widely used as a treatment of venous thromboembolism and its capability to reduce the hazard of thromboembolic events has been unequivocally demonstrated. Variability between individuals, as well as a narrow therapeutic range are barriers to safe and effective warfarin therapy. Inadequate dose individualization contributes to under-utilization, 18-55% of patients who would benefit […]

Total and unbound mycophenolic acid pharmacokinetics before and after kidney transplantation

Background: An increased incidence of acute rejection is seen with underexposure to mycophenolic acid (MPA) in the initial week post kidney transplantation, particularly in high immunological risk patients (1,2). Up to 25% of individuals in contemporary drug regimens are below the proposed therapeutic range at this time (3), and these individuals cannot be identified a […]

Study designs for renal drug studies

Introduction: Renal dose adjustment generally assumes a linear relationship between renal drug clearance and glomerular filtration rate (GFR). The theory underpinning this practice is the Intact Nephron Hypothesis (INH) [1], which assumes that nephrons are either completely functional (intact) or completely non-functional. There is a growing body of evidence to suggest that a non-linear relationship […]