Population Pharmacokinetics of Rivaroxaban in Real-World Patients

The pharmacokinetics (PK) of rivaroxaban have been studied in different populations, and there were differences in the PK parameters. However, most of these studies were conducted on healthy subjects from different ethnic groups. Thus, this study aimed to investigate the PK of rivaroxaban in real-world patients to determine the covariates that may cause differences in the pharmacokinetics of rivaroxaban. This was a prospective observational study. Five blood samples were collected at different time points after starting the rivaroxaban dose. Plasma concentrations were analyzed, and population PK models were developed using Monolix version 4.4 software. In total, 100 blood samples from 20 patients (50% men/50% women) were analyzed. The patients' mean (±standard deviation) age was 53.1 (±15.5) years and their mean body weight was 81.7 (±27.2) kg. The PK of rivaroxaban were described by a 1-compartment model. The initial estimates for the absorption rate constant, apparent clearance (CL/F), and apparent volume of distribution were 1.8/h, 4.46 L/h, and 21.7 L, respectively. The interindividual variability for absorption rate constant, CL/F, and volume of distribution was 14%, 24%, and 29.3%, respectively. Covariates were tested for their influence on rivaroxaban pharmacokinetics. The aspartate aminotransferase, alanine aminotransferase, body mass index, and albumin concentrations had an effect on the CL/F of rivaroxaban. In this analysis, the population PK model of rivaroxaban found significant interindividual variability. Several covariates influenced the clearance of rivaroxaban and contributed to this variability. The results may provide a guide that can aid the clinician during the initiation and adjustment of therapeutic regimens.