Trial reportCardiovascular drugs and therapy2024
Effect of Clarithromycin, a Strong CYP3A and P-glycoprotein Inhibitor, on the Pharmacokinetics of Edoxaban in Healthy Volunteers and the Evaluation of the Drug Interaction with Other Oral Factor Xa Inhibitors by a Microdose Cocktail Approach.
Trial report in Cardiovascular drugs and therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- Literature-based case analysis of serious adverse drug events associated with edoxaban.European journal of clinical pharmacology · 2025Pooled it
- Time Course of the Interaction Between Oral Short-Term Ritonavir Therapy with Three Factor Xa Inhibitors and the Activity of CYP2D6, CYP2C19, and CYP3A4 in Healthy Volunteers.Clinical pharmacokinetics · 2024Trial
- Pharmacokinetic Variability of Direct Oral Anticoagulants and Calcium Channel Blockers: A Comparative Analysis of Exposure Data from Clinical Studies.Pharmaceutics · 2026Article
- Suzetrigine Is Not Expected to Have Clinically Relevant DDIs with Apixaban and Rivaroxaban Based on PBPK Modeling.Journal of clinical pharmacology · 2026Article
- Effect of enzalutamide on anticoagulant therapy with edoxaban in patients with prostate cancer.British journal of clinical pharmacology · 2026Article
- Effect of the frequently used antiepileptic drugs carbamazepine, gabapentin, and pregabalin on the pharmacokinetics of edoxaban and other oral factor xa inhibitors in healthy volunteers.Frontiers in pharmacology · 2025Article
- Impact of anti-peptic ulcer disease medications on type 2 diabetes mellitus risk in patients with PUD: a population-based retrospective cohort study.Therapeutic advances in endocrinology and metabolism · 2025Article
- Evaluation of Drug-Drug Interactions Between Clarithromycin and Direct Oral Anticoagulants Using Physiologically Based Pharmacokinetic Models.Pharmaceutics · 2024Article
- 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
- Extracellular Vesicles as Surrogates for the Regulation of the Drug Transporters ABCC2 (MRP2) and ABCG2 (BCRP).International journal of molecular sciences · 2024Article
- Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWe assessed the differential effect of clarithromycin, a strong inhibitor of cytochrome P450 (CYP) 3A4 and P-glycoprotein, on the pharmacokinetics of a regular dose of edoxaban and on a microdose cocktail of factor Xa inhibitors (FXaI). Concurrently, CYP3A activity was determined with a midazolam microdose.
methodsIn an open-label fixed-sequence trial in 12 healthy volunteers, the pharmacokinetics of a microdosed FXaI cocktail (μ-FXaI; 25 μg apixaban, 50 μg edoxaban, and 25 μg rivaroxaban) and of 60 mg edoxaban before and during clarithromycin (2 x 500 mg/d) dosed to steady-state was evaluated. Plasma concentrations of study drugs were quantified using validated ultra-performance liquid chromatography-tandem mass spectrometry methods.
resultsTherapeutic clarithromycin doses increased the exposure of a therapeutic 60 mg dose of edoxaban with a geometric mean ratio (GMR) of the area under the plasma concentration-time curve (AUC) of 1.53 (90 % CI: 1.37-1.70; p < 0.0001). Clarithromycin also increased the GMR (90% CI) of the exposure of microdosed FXaI apixaban to 1.38 (1.26-1.51), edoxaban to 2.03 (1.84-2.24), and rivaroxaban to 1.44 (1.27-1.63). AUC changes observed for the therapeutic edoxaban dose were significantly smaller than those observed with the microdose (p < 0.001).
conclusionClarithromycin increases FXaI exposure. However, the magnitude of this drug interaction is not expected to be clinically relevant. The edoxaban microdose overestimates the extent of the drug interaction with the therapeutic dose, whereas AUC ratios for apixaban and rivaroxaban were comparable to the interaction with therapeutic doses as reported in the literature.
trial registrationEudraCT Number: 2018-002490-22.
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