Trial reportBritish journal of clinical pharmacology2015
Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor.
Trial report in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 6 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
81 citing papers in PubMed, 6 syntheses or guidelines pooled it, 158 citations in OpenAlex.
- 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.Journal of the American College of Cardiology · 2024Guideline
- Guideline
- Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Patients with Atrial Fibrillation Using P-gp and/or CYP450-Interacting Drugs: a Systematic Review and Meta-analysis.Cardiovascular drugs and therapy · 2023Pooled it
- Drug interactions with apixaban: A systematic review of the literature and an analysis of VigiBase, the World Health Organization database of spontaneous safety reports.Pharmacology research & perspectives · 2020Pooled it
- Drug-drug interactions with direct oral anticoagulants associated with adverse events in the real world: A systematic review.Thrombosis research · 2020Pooled it
- Intestinal Efflux Transporters P-gp and BCRP Are Not Clinically Relevant in Apixaban Disposition.Pharmaceutical research · 2020Pooled it
- 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.Cardiovascular drugs and therapy · 2024Trial
- Pharmacokinetics of apixaban and tacrolimus or cyclosporine in kidney and lung transplant recipients.Clinical and translational science · 2022Trial
- Perpetrator Characteristics of Azole Antifungal Drugs on Three Oral Factor Xa Inhibitors Administered as a Microdosed Cocktail.Clinical pharmacokinetics · 2022Trial
- Microdosed Cocktail of Three Oral Factor Xa Inhibitors to Evaluate Drug-Drug Interactions with Potential Perpetrator Drugs.Clinical pharmacokinetics · 2019Trial
- Drug-Drug Interaction Study of Apixaban with Cyclosporine and Tacrolimus in Healthy Volunteers.Clinical and translational science · 2018Trial
- Population Pharmacokinetics, Pharmacodynamics, and Exploratory Exposure-Response Analyses of Apixaban in Subjects Treated for Venous Thromboembolism.CPT: pharmacometrics & systems pharmacology · 2017Trial
- Suzetrigine Is Not Expected to Have Clinically Relevant DDIs with Apixaban and Rivaroxaban Based on PBPK Modeling.Journal of clinical pharmacology · 2026Article
- A 3-step static mechanistic modeling approach to predicting transporter- and enzyme-mediated interaction signals of direct oral anticoagulants.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Risk of opioid overdose associated with concurrent use of hydrocodone and CYP3A4-inhibiting calcium channel blockers: a population-based cohort study.American journal of epidemiology · 2025Article
- Real-World Use and Outcomes of Apixaban for Early Post-Surgical Fontan Thromboprophylaxis.Pediatric cardiology · 2025Article
- Real-World Impact of Amiodarone on Apixaban Population Pharmacokinetics in Hospitalized Patients.Clinical and translational science · 2025Article
- In vivo Pharmacokinetic Interactions Between Palbociclib and Rivaroxaban or Apixaban: Implications for Increased Drug Exposure and Dose Adjustments.Drug design, development and therapy · 2025Article
- The Role of ABCB1, ABCG2, and SLC Transporters in Pharmacokinetic Parameters of Selected Drugs and Their Involvement in Drug-Drug Interactions.Membranes · 2024Review
- Impact of posaconazole and diltiazem on pharmacokinetics of encorafenib, a BRAF V600 kinase inhibitor for melanoma and colorectal cancer with BRAF mutations.Clinical and translational science · 2023Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimApixaban is an orally active inhibitor of coagulation factor Xa and is eliminated by multiple pathways, including renal and non-renal elimination. Non-renal elimination pathways consist of metabolism by cytochrome P450 (CYP) enzymes, primarily CYP3A4, as well as direct intestinal excretion. Two single sequence studies evaluated the effect of ketoconazole (a strong dual inhibitor of CYP3A4 and P-glycoprotein [P-gp]) and diltiazem (a moderate CYP3A4 inhibitor and a P-gp inhibitor) on apixaban pharmacokinetics in healthy subjects.
methodIn the ketoconazole study, 18 subjects received apixaban 10 mg on days 1 and 7, and ketoconazole 400 mg once daily on days 4-9. In the diltiazem study, 18 subjects received apixaban 10 mg on days 1 and 11 and diltiazem 360 mg once daily on days 4-13.
resultsApixaban maximum plasma concentration and area under the plasma concentration-time curve extrapolated to infinity increased by 62% (90% confidence interval [CI], 47, 78%) and 99% (90% CI, 81, 118%), respectively, with co-administration of ketoconazole, and by 31% (90% CI, 16, 49%) and 40% (90% CI, 23, 59%), respectively, with diltiazem.
conclusionA 2-fold and 1.4-fold increase in apixaban exposure was observed with co-administration of ketoconazole and diltiazem, respectively.
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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.