Trial reportClinical pharmacokinetics2022
Perpetrator Characteristics of Azole Antifungal Drugs on Three Oral Factor Xa Inhibitors Administered as a Microdosed Cocktail.
Trial report in Clinical pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- 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
- Suzetrigine Is Not Expected to Have Clinically Relevant DDIs with Apixaban and Rivaroxaban Based on PBPK Modeling.Journal of clinical pharmacology · 2026Article
- A Single Health System Retrospective Qualitative Analysis of Inpatient Apixaban and Rivaroxaban Calibrated Anti-Xa Level Monitoring and Clinical Implications.Hospital pharmacy · 2026Article
- Characterizing Apixaban Pharmacokinetics Through Physiologically-Based Pharmacokinetic Modeling: Critical Role of Biliary Secretion and Enterohepatic Circulation in Humans.CPT: pharmacometrics & systems pharmacology · 2026Article
- Drug-Drug Interactions Between Direct Oral Anticoagulants and Other Medications in Patients with Pulmonary Embolism: Results from the Lungenembolie Augsburg (LEA).Clinical pharmacokinetics · 2025Article
- Article
- Understanding CYP3A4 and P-gp mediated drug-drug interactions through PBPK modeling - Case example of pralsetinib.CPT: pharmacometrics & systems pharmacology · 2024Article
- Pharmacokinetics of a microdosed cocktail of three direct oral anticoagulants in children with congenital heart defects: study protocol for a single-centre clinical trial (DOAC-Child).BMJ paediatrics open · 2023Article
- Impact of concomitant fluconazole on direct oral anticoagulant bleeding risk.Pharmacotherapy · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFactor Xa inhibitors (FXaIs) are increasingly used without having sufficient drug-drug interaction data. Using a microdosed cocktail methodology could support filling the knowledge gap quickly.
methodsIn a randomised crossover trial, we investigated the drug-drug interactions between six oral azole antifungals and a microdosed FXaI cocktail containing 25 µg rivaroxaban, 25 µg apixaban, and 50 µg edoxaban. Additionally, different enzyme activities were also monitored using a microdosed cocktail approach. The six different azole antifungals were administered in therapeutic doses over a 24 h period, while the microdosed cocktails were administered 1 h after administration of the azole antifungals.
resultsKetoconazole and posaconazole were the strongest perpetrators, showing similar increases as apixaban (area under the concentration-time curve ratio [AUCR] 1.64 and 1.62, respectively) and edoxaban (AUCR 2.08 and 2.1, respectively), whereas ketoconazole increased rivaroxaban 2.32-fold but only increased posaconazole 1.37-fold. All other azole antifungals showed less perpetrator effects on the FXaIs. Cytochrome P450 (CYP) 3A inhibition was confirmed using microdosed midazolam, with ketoconazole also the most potent perpetrator (8.42-fold).
conclusionDrug-drug interactions for three victim drugs of the same drug class (FXaIs) with different clearance mechanisms can be studied using a microdosed cocktail approach. Using members of the azole antifungal drug class as perpetrators, multiple interactions can be studied in one trial, and a more detailed insight into the underlying interaction mechanisms is possible. CLINICAL
trial registrationEudraCT number: 2017-004453-16.
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