ArticleEuropean journal of clinical pharmacology2019
Downregulation of ABCB1 gene in patients with total hip or knee arthroplasty influences pharmacokinetics of rivaroxaban: a population pharmacokinetic-pharmacodynamic study.
Article in European journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Population Pharmacokinetic Models for Direct Oral Anticoagulants: A Systematic Review and Clinical Appraisal Using Exposure Simulation.Clinical pharmacology and therapeutics · 2022Pooled it
- Population pharmacokinetics of rivaroxaban after transjugular intrahepatic portosystemic shunt.European journal of clinical pharmacology · 2026Article
- Pharmacogenomics in the prediction of adverse effects of cardiovascular drugs: the PGx-CardioDrug project.Croatian medical journal · 2026Review
- Population pharmacokinetics and pharmacogenomics of edoxaban in Japanese adults with atrial fibrillation.Journal of pharmaceutical health care and sciences · 2025Article
- Population pharmacokinetic analysis of rivaroxaban in healthy volunteers and patients with radiofrequency ablation of non-valvular atrial fibrillation in China.Frontiers in pharmacology · 2025Article
- Population pharmacokinetics of rivaroxaban in Chinese deep vein thrombosis patients and the exposure simulation for dosing recommendation.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- The impact of ABCB1, CYP3A4/5 and ABCG2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non-valvular atrial fibrillation.Human genomics · 2023Article
- Personalizing Direct Oral Anticoagulant Therapy for a Diverse Population: Role of Race, Kidney Function, Drug Interactions, and Pharmacogenetics.Clinical pharmacology and therapeutics · 2023Review
- Review
- Is a Lower Dose of Rivaroxaban Required for Asians? A Systematic Review of a Population Pharmacokinetics and Pharmacodynamics Analysis of Rivaroxaban.Pharmaceutics · 2023Review
- Population Pharmacokinetics and Dose Optimization Based on Renal Function of Rivaroxaban in Thai Patients with Non-Valvular Atrial Fibrillation.Pharmaceutics · 2022Article
- Article
- A Combined Pharmacometrics Analysis of Biomarker Distribution Under Treatment With Standard- or Low-Dose Rivaroxaban in Real-World Chinese Patients With Nonvalvular Atrial Fibrillation.Frontiers in pharmacology · 2022Article
- Use of pharmacogenomics in elderly patients treated for cardiovascular diseases.Croatian medical journal · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
purposeRivaroxaban is a substrate for ABCB1 transporter and is commonly used in patients undergoing hip or knee replacement surgery for thromboprophylaxis. The objective of this study was to develop a population pharmacokinetic-pharmacodynamic (PK-PD) model to investigate the influence of ABCB1 gene expression and polymorphism on rivaroxaban exposure and anticoagulation effects.
methodsFive blood samples per patient were collected during 5 days after the surgery for the determination of rivaroxaban concentration in plasma and for determination of prothrombin time and partial thromboplastin time. Non-linear mixed effects model was used for a population PK-PD analysis and for testing covariate effects.
resultsA one-compartment PK model with first-order absorption adequately described the pharmacokinetic data. The typical oral clearance (CL/F) was 6.12 L/h (relative standard error, 15.8%) and was associated with ABCB1 expression. Compared to base line before the surgery, a significant ABCB1 downregulation was observed 5 days after the surgery (p < 0.001). Prothrombin time and partial thromboplastin time were both linearly associated to the logarithm of the rivaroxaban plasma concentration.
conclusionsWe confirmed that variable rivaroxaban CL/F is associated with ABCB1 expression, which is in accordance with previous studies on P-glycoprotein involvement in rivaroxaban PK. Furthermore, we observed the downregulation of ABCB1 expression after the surgery. The cause remains unclear and further research is needed to explain the underlying mechanisms.
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