Integrated Population Pharmacokinetic Analysis of Rivaroxaban Across Multiple Patient Populations

• Published in: CPT: pharmacometrics and systems pharmacology Vol. 7; no. 5; pp. 309 - 320
• Main Authors: Willmann, Stefan, Zhang, Liping, Frede, Matthias, Kubitza, Dagmar, Mueck, Wolfgang, Schmidt, Stephan, Solms, Alexander, Yan, Xiaoyu, Garmann, Dirk
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.05.2018; John Wiley and Sons Inc
• Subjects: Age; Anticoagulants; Clinical trials; Drug dosages; Embolisms; Joint replacement surgery; Patients; Pharmacokinetics; Prevention; R&D; Research & development; Stroke; Studies; United States > US
• ISSN: 2163-8306; 2163-8306
• DOI: 10.1002/psp4.12288

The population pharmacokinetics (PK) of rivaroxaban have been evaluated in several population‐specific models. We developed an integrated population PK model using pooled data from 4,918 patients in 7 clinical trials across all approved indications. Effects of gender, age, and weight on apparent clearance (CL/F) and apparent volume of distribution (V/F), renal function, and comedication on CL/F, and relative bioavailability as a function of dose (F) were analyzed. Virtual subpopulations for exposure simulations were defined by age, creatinine clearance (CrCL) and body mass index (BMI). Rivaroxaban PK were adequately described by a one‐compartment disposition model with a first‐order absorption rate constant. Significant effects of CrCL, use of comedications, and study population on CL/F, age, weight, and gender on V/F, and dose on F were identified. CrCL had a modest influence on exposure, whereas age and BMI had a minor influence. The model was suitable to predict rivaroxaban exposure in patient subgroups of special interest.