Population pharmacokinetics of rivaroxaban in Chinese deep vein thrombosis patients and the exposure simulation for dosing recommendation.

Abstract

This study aimed to develop a population pharmacokinetic (PPK) model for rivaroxaban and establish a model-based dosing guideline tailored to Chinese patients with deep vein thrombosis (DVT). A nonlinear mixed-effects modeling approach was employed using Phoenix NLME 7.0 software to construct the PPK model for rivaroxaban. The PK of rivaroxaban was adequately characterized through a one-compartment model. Monte Carlo simulations were employed to formulate dosing guidelines applicable to different patient subgroups. Data from 60 Chinese DVT patients yielded 217 rivaroxaban plasma concentrations for analysis. The apparent clearance (CL/F) of rivaroxaban was found to be significantly influenced by the estimated glomerular filtration rate (eGFR), identified as a major covariate. Based on Monte Carlo simulations, for the acute DVT treatment, a regimen of 15mg, 10mg, or 5mg twice daily was associated with the highest total probability target attainment (PTAtotal) in patients with normal, mildly impaired, or moderately impaired renal function, respectively. For the continued DVT treatment, a regimen of 20mg, 15mg, or 5mg once daily exhibited the maximum PTAtotal in patients with normal, mildly impaired, or moderately impaired renal function, respectively. The recommendation label dose achieved the PK target in those with normal renal function. However, for patients with mild or moderate renal impairment, dose adjustments below the label recommendation might be necessary. The PPK model associated CL/F with the covariate eGFR. Utilizing the PPK model, a dosage regimen table was constructed to offer tailored dosing recommendations for Chinese DVT patients.