The impact of body weight on rivaroxaban pharmacokinetics

Background: There is concern amongst clinicians that the fixed dosing strategy of rivaroxaban for the treatment of venous thromboembolism (VTE) might not be optimal in those patients under or overweight. Objective: To develop a pharmacokinetic model for rivaroxaban, based on real-world patients, specifically focusing on the impact of patients' body weight on rivaroxaban pharmacokinetics. Patients/methods: One hundred and one patients prescribed rivaroxaban prophylactic or treatment doses for the prevention or treatment of VTE were recruited at a London teaching hospital. Subjects had up to 3 rivaroxaban concentrations measured during a single dosing period (trough, 1 and 3 hours post dose). Population pharmacokinetic analyses was conducted to develop a rivaroxaban model, which was subsequently evaluated. Results: A one-compartment model with between-subject variability on rivaroxaban clearance and volume of distribution, with a combined (additive and proportional) error model, best fitted the data. Following a full covariate analysis, creatinine clearance on rivaroxaban clearance was found to be the significant covariate impacting on the pharmacokinetic profile of rivaroxaban in the dataset. Conclusions: Our results suggest that the most important covariate impacting on rivaroxaban pharmacokinetics is creatinine clearance and the weight alone has little effect. These findings are in line with previous studies for rivaroxaban. Larger datasets, from real-world patients who are followed longitudinally, should be conducted to provide front-line clinicians with further reassurance when prescribing rivaroxaban for the acute management of VTE.