ArticleCPT: pharmacometrics & systems pharmacology2023
Physiologically-based pharmacokinetic pharmacodynamic parent-metabolite model of edoxaban to predict drug-drug-disease interactions: M4 contribution.
Article in CPT: pharmacometrics & systems pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- Development of an isavuconazole physiologically-based pharmacokinetic model for adult and pediatric populations.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Drug-Drug Interactions Between Oral Anticoagulants and Calcineurin Inhibitors in Nephrotic Syndrome for Management of Thromboembolism.Biomedicines · 2026Review
- Effect of enzalutamide on anticoagulant therapy with edoxaban in patients with prostate cancer.British journal of clinical pharmacology · 2026Article
- Characterizing Apixaban Pharmacokinetics Through Physiologically-Based Pharmacokinetic Modeling: Critical Role of Biliary Secretion and Enterohepatic Circulation in Humans.CPT: pharmacometrics & systems pharmacology · 2026Article
- Abnormally high plasma concentrations of M-4, the active metabolite of edoxaban, at the onset of acute kidney injury in a patient receiving rifampin and clarithromycin: a case report.Journal of pharmaceutical health care and sciences · 2024Article
- Physiologically-based pharmacokinetic pharmacodynamic parent-metabolite model of edoxaban to predict drug-drug-disease interactions: M4 contribution.CPT: pharmacometrics & systems pharmacology · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study aimed to develop a physiologically-based pharmacokinetic pharmacodynamic (PBPK/PD) parent-metabolite model of edoxaban, an oral anticoagulant with a narrow therapeutic index, and to predict pharmacokinetic (PK)/PD profiles and potential drug-drug-disease interactions (DDDIs) in patients with renal impairment. A whole-body PBPK model with a linear additive PD model of edoxaban and its active metabolite M4 was developed and validated in SimCYP for healthy adults with or without interacting drugs. The model was extrapolated to situations including renal impairment and drug-drug interactions (DDIs). Observed PK and PD data in adults were compared with predicted data. The effect of several model parameters on the PK/PD response of edoxaban and M4 was investigated in sensitivity analysis. The PBPK/PD model successfully predicted PK profiles of edoxaban and M4 as well as anticoagulation PD responses with or without the influence of interacting drugs. For patients with renal impairment, the PBPK model successfully predicted the fold change in each impairment group. Inhibitory DDI and renal impairment had a synergistic effect on the increased exposure of edoxaban and M4, and their downstream anticoagulation PD effect. Sensitivity analysis and DDDI simulation show that renal clearance, intestinal P-glycoprotein activity, and hepatic OATP1B1 activity are the major factors affecting edoxaban-M4 PK profiles and PD responses. Anticoagulation effect induced by M4 cannot be ignored when OATP1B1 is inhibited or downregulated. Our study provides a reasonable approach to adjust the dose of edoxaban in several complicated scenarios especially when M4 cannot be ignored due to decreased OATP1B1 activity.
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