Population Pharmacokinetics of Rivaroxaban in Chinese Patients with Non-Valvular Atrial Fibrillation: A Prospective Multicenter Study

Zhang, Feilong; Chen, Xuehai; Wu, Tingting; Huang, Nianxu; Li, Li; Yuan, Dandan; Xiang, Jing; Wang, Na; Zhang, Jinhua

doi:10.1007/s40262-022-01108-3

Cited by 10 publications

(33 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the covariate analysis, the final model revealed that CL/F and V/F of rivaroxaban increase by increasing CrCl and body weight, respectively. Several previous studies showed the significant effect of CrCl on rivaroxaban CL/F [20,24,34,[39][40][41][42], thus, our finding confirmed this relationship. Because rivaroxaban is partly excreted through the kidneys, reduced renal function results in lower drug clearance [19].…”

Section: Discussionsupporting

confidence: 90%

“…The rivaroxaban PK in Thai DOAC-eligible AF patients was adequately described by a one-compartment model with first-order absorption and elimination, consistent with previous studies in AF patients [20,23,24,33,34,37]. The estimation of CL/F (4.19 L/h) in Thai DOAC-eligible AF patients was slightly lower than that reported in other ethnicities, including Caucasians (5.58-6.10 L/h) [20,37].…”

Section: Discussionsupporting

confidence: 83%

“…The estimation of CL/F (4.19 L/h) in Thai DOAC-eligible AF patients was slightly lower than that reported in other ethnicities, including Caucasians (5.58-6.10 L/h) [20,37]. When compared to other Asian populations, the CL/F in this study is comparable to Japanese (4.72-4.73 L/h) [23,24] but lower than Chinese (5.03-7.39 L/h) [33,34,38]. The estimated V/F (37.5 L) was lower than that reported in other studies (40.3-79.7 L) [23,24,33,34,37].…”

Section: Discussioncontrasting

confidence: 67%

“…When compared to other Asian populations, the CL/F in this study is comparable to Japanese (4.72-4.73 L/h) [23,24] but lower than Chinese (5.03-7.39 L/h) [33,34,38]. The estimated V/F (37.5 L) was lower than that reported in other studies (40.3-79.7 L) [23,24,33,34,37]. The discrepancies in PK values between ethnic groups might be attributable to variability in patient characteristics.…”

Section: Discussionsupporting

confidence: 44%

“…The renal function of Asian patients with AF, as measured by CrCl, was lower than that of Caucasians [31,32]. As a result, it is likely that a lower dose of rivaroxaban gives enough exposure for Asians [23,24,33,34], reducing the risk of bleeding [5,35]. However, the PK data needed to optimize doses in Thai and Asian populations is scarce.…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

Population Pharmacokinetics and Dose Optimization Based on Renal Function of Rivaroxaban in Thai Patients with Non-Valvular Atrial Fibrillation

et al. 2022

View full text Add to dashboard Cite

Low-dose rivaroxaban has been used in Asian patients with direct oral anticoagulants (DOACs) eligible for atrial fibrillation (AF). However, there are few pharmacokinetic (PK) data in Thai patients to support precise dosing. This study aimed to develop a population PK model and determine the optimal rivaroxaban doses in Thai patients. A total of 240 Anti-Xa levels of rivaroxaban from 60 Thai patients were analyzed. A population PK model was established using the nonlinear mixed-effect modeling approach. Monte Carlo simulations were used to predict drug exposures at a steady state for various dosages. Proportions of patients having rivaroxaban exposure within typical exposure ranges were determined. A one-compartment model with first-order absorption best described the data. Creatinine clearance (CrCl) and body weight significantly affected CL/F and V/F, respectively. Regardless of body weight, a higher proportion of patients with CrCl < 50 mL/min receiving the 10-mg once-daily dose had rivaroxaban exposures within the typical exposure ranges. In contrast, a higher proportion of patients with CrCl ≥ 50 mL/min receiving the 15-mg once-daily dose had rivaroxaban exposures within the typical exposure ranges. The study’s findings suggested that low-dose rivaroxaban would be better suited for Thai patients and suggested adjusting the medication’s dose in accordance with renal function.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 83%

Section: Discussioncontrasting

confidence: 67%

Section: Discussionsupporting

confidence: 44%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Population Pharmacokinetics and Dose Optimization Based on Renal Function of Rivaroxaban in Thai Patients with Non-Valvular Atrial Fibrillation

et al. 2022

View full text Add to dashboard Cite

show abstract

Population Pharmacokinetics and Hemorrhagic Risk Analysis of Rivaroxaban in Elderly Chinese Patients With Nonvalvular Atrial Fibrillation

Zhang

Chen

Qin

et al. 2022

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Rivaroxaban is a popular direct factor Xa inhibitor used for anticoagulation therapy in patients with nonvalvular atrial fibrillation (NVAF). The aim of this study was to establish a population pharmacokinetic (PPK) model for rivaroxaban in elderly Chinese patients with nonvalvular atrial fibrillation, evaluate precision dosing regimens, and analyze hemorrhagic risk after rivaroxaban treatment. A 1-compartment population PK model with estimated glomerular filtration rate (eGFR), total bilirubin (TBIL), and ABCB1 rs1045642 as major covariates for apparent clearance was developed using the nonlinear mixed-effects model (NONMEM). A Monte Carlo simulation was performed to evaluate various dosing schemes and different levels of covariates for the target range of therapeutic drug-monitoring concentrations (C max,ss and C min,ss ). The exposure to rivaroxaban was simulated and assessed through hemorrhagic risk evaluation. The results showed that the average probability of target attainment (PTA) for optimal dosing regimens with different covariate levels for the targeted C max,ss and C min,ss were 29.35% to 31.3% and 64.91% to 65.8%, respectively. A dosage of 10 mg of rivaroxaban in elderly Chinese patients with normal renal and liver function was appropriate. The area under the concentration-time curve estimated over 24 hours with precision dosing at steady state (AUC 24,ss ) was statistically significantly associated with an increased risk of bleeding events (OR 1.0006, 95%CI 1.0003 to 1.001, P < .0001), and the bleeding risk increased by 1.82-fold for every 1000 μg*h/L increase in AUC 24,ss . A lower dose is recommended for elderly patients with renal impairment to avoid overexposure and bleeding events. The PPK model could inform individualized dosing for elderly Chinese patients with nonvalvular atrial fibrillation receiving rivaroxaban anticoagulation therapy.

show abstract

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

Li,

Yang,

Hua

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

Population Pharmacokinetics of Rivaroxaban in Chinese Patients with Non-Valvular Atrial Fibrillation: A Prospective Multicenter Study

Cited by 10 publications

References 32 publications

Population Pharmacokinetics and Dose Optimization Based on Renal Function of Rivaroxaban in Thai Patients with Non-Valvular Atrial Fibrillation

Population Pharmacokinetics and Dose Optimization Based on Renal Function of Rivaroxaban in Thai Patients with Non-Valvular Atrial Fibrillation

Population Pharmacokinetics and Hemorrhagic Risk Analysis of Rivaroxaban in Elderly Chinese Patients With Nonvalvular Atrial Fibrillation

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

Contact Info

Product

Resources

About