Trial reportClinical pharmacokinetics2016
Population Pharmacokinetics of Edoxaban in Patients with Non-Valvular Atrial Fibrillation in the ENGAGE AF-TIMI 48 Study, a Phase III Clinical Trial.
Trial report in Clinical pharmacokinetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 4 syntheses or guidelines pooled it, 32 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
- Model-based meta-analysis to evaluate optimal doses of direct oral factor Xa inhibitors in atrial fibrillation patients.Blood advances · 2018Pooled it
- Direct oral anticoagulants versus warfarin for preventing stroke and systemic embolic events among atrial fibrillation patients with chronic kidney disease.The Cochrane database of systematic reviews · 2017Pooled it
- The non-vitamin K antagonist oral anticoagulants (NOACs) and extremes of body weight-a systematic literature review.Clinical research in cardiology : official journal of the German Cardiac Society · 2017Pooled it
- Population pharmacokinetics and pharmacogenomics of edoxaban in Japanese adults with atrial fibrillation.Journal of pharmaceutical health care and sciences · 2025Article
- Insights into the Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants in Older Adults with Atrial Fibrillation: A Structured Narrative Review.Clinical pharmacokinetics · 2023Review
- Low Exposure to Direct Oral Anticoagulants Is Associated with Ischemic Stroke and Its Severity.Journal of stroke · 2022Article
- High incidence of major bleeding with off-label use of edoxaban.Journal of clinical biochemistry and nutrition · 2021Article
- Treatment with Edoxaban Attenuates Acute Stroke Severity in Mice by Reducing Blood-Brain Barrier Damage and Inflammation.International journal of molecular sciences · 2021Article
- Edoxaban and the Issue of Drug-Drug Interactions: From Pharmacology to Clinical Practice.Drugs · 2020Review
- Effect of the number of dose adjustment factors on bleeding risk in patients receiving 30 mg/day edoxaban.Journal of clinical pharmacy and therapeutics · 2020Article
- Integrated Population Pharmacokinetic Analysis of Rivaroxaban Across Multiple Patient Populations.CPT: pharmacometrics & systems pharmacology · 2018Article
- Direct oral anticoagulant considerations in solid organ transplantation: A review.Clinical transplantation · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionEdoxaban is a novel factor Xa inhibitor. This study characterizes the population pharmacokinetics of edoxaban in patients with non-valvular atrial fibrillation (NVAF) included in the phase III ENGAGE AF-TIMI 48 study, evaluates covariates for the dose-exposure relationship in this population, and assesses the impact of protocol-specified dose reductions on exposure using simulations.
methodsModel development was performed using NONMEM(®) and based on sparse data from the ENGAGE AF-TIMI 48 study augmented with dense data from 13 phase I studies to inform and stabilize the model. The influence of body weight (WT), creatinine clearance (CLCR), concomitant P-glycoprotein (P-gp) inhibitors, age, sex, race, and NVAF on pharmacokinetic parameters was evaluated based on statistical significance and clinical relevance.
resultsA two-compartment model with first-order elimination and first-order absorption after an absorption lag-time best described the data. Apparent volume and clearance terms increased with increasing WT. Apparent renal clearance increased with increasing CLCR. Apparent non-renal, renal, and inter-compartmental clearance terms differed between phase I volunteers and NVAF patients. Asian patients were found to have increased apparent central volume of distribution, bioavailability, and total apparent clearance. Concomitant P-gp inhibitors increased the bioavailability statistically significantly, but this did not reach clinical relevance.
conclusionEdoxaban disposition and the variability in this disposition, including influence of covariates, after oral administration were adequately characterized in patients with NVAF. The 50 % dose reduction in patients with low WT (≤60 kg), moderate renal impairment (CLCR ≤50 mL/min), or concomitant P-gp inhibitors led to 30 % lower exposure than in the other patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.