Drug Des Devel Ther. 2025 Dec 3;19:10703-10717. doi: 10.2147/DDDT.S563521. eCollection 2025.
ABSTRACT
PURPOSE: This study aimed to develop a population pharmacokinetic (PopPK) model in elderly Chinese patient with NVAF, characterize the pharmacokinetic variability, identify relevant covariates affecting rivaroxaban disposition, and explore the exposure-response relationship.
PATIENTS AND METHODS: A prospective observational study was conducted with rivaroxaban plasma samples collected and analyzed. A PopPK model was developed using the nonlinear mixed-effects modeling approach. Monte Carlo simulations were employed to explore the correlation between significant covariates and estimated drug exposure. AUC24,ss derived from the PopPK analysis, was computed to evaluate exposure-response relationships.
RESULTS: Ninety-three elderly Chinese NVAF patients contributed 256 plasma concentrations were well described by a one-compartment PopPK model. Creatinine clearance (CrCL) and concomitant use of amiodarone were identified as significantly influencing clearance (CL). The simulation results revealed the following: (1) For patients with normal or mildly impaired renal function (CrCL ≥50 mL/min), both a 20 mg once-daily dosage without amiodarone and a 10 mg with amiodarone were acceptable; (2) For those with moderate to severe renal impairment (CrCL 15-49 mL/min), a 10 mg once-daily dosage was appropriate regardless of amiodarone coadministration; (3) Although a 15 mg once-daily dosage was generally suitable from the pharmacokinetic standpoint, concomitant use of amiodarone significantly increased bleeding risk in patients (RR = 8.00, p = 0.039); (4) AUC24,ss was significantly decreased in patients with thromboembolic events compared to those without such events (p < 0.0001), with 2840 ng·h/mL identified as the optimal cut-off value (p = 0.023).
CONCLUSION: For elderly Chinese NVAF patients, a reduced-dose rivaroxaban regimen, specifically 10 mg once daily with amiodarone, is recommended for all patients regardless of renal function, whereas 15 mg once daily is a more optimal option for those not taking amiodarone. Based on the risk-benefit assessment, maintaining AUC24,ss above 2840 ng·h/mL does not yield additional clinical benefit.
PMID:41368590 | PMC:PMC12683255 | DOI:10.2147/DDDT.S563521