Evidence map›Paper›PMID 23305158›Full record

Trial reportBritish journal of clinical pharmacology2013

Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects.

Wolfgang Mueck, Dagmar Kubitza, Michael Becka

Registry-linked trialOpen access · bronzeAbstract readClinical TrialMulticenter Study
In one paragraph

Trial report in British journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03864406 (Impact of Steady State Cobicistat and Darunavir/Cobicistat on the Pharmacokinetics and Pharmacodynamics of Oral Anticoagulants), which is not on this map. Cited by 180 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
180citing papers in PubMed, 8 pooled it
19.6field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT03864406 phase1completednot on this mapstarted 2019, after this paper: background citation

Impact of Steady State Cobicistat and Darunavir/Cobicistat on the Pharmacokinetics and Pharmacodynamics of Oral Anticoagulants (Rivaroxaban, Apixaban) in Healthy Volunteers

TypeinterventionalSponsorNational Institutes of Health Clinical Center (CC)Ran2019 to 2022Enrolled12ConditionsHealthy VolunteersArmsCobicistat, Darunavir/Cobicistat, Rivaroxaban
3 · Its place in the literature

Who cites it

180 citing papers in PubMed, 8 syntheses or guidelines pooled it, 364 citations in OpenAlex.

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  7. The influence of bariatric surgery on oral drug bioavailability in patients with obesity: A systematic review.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2019
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120 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Wolfgang MueckBayer HealthCare Pharmaceuticals, Wuppertal, Germany.
Dagmar Kubitza
Michael Becka
Bayer (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThe anticoagulant rivaroxaban is an oral, direct Factor Xa inhibitor for the management of thromboembolic disorders. Metabolism and excretion involve cytochrome P450 3A4 (CYP3A4) and 2J2 (CYP2J2), CYP-independent mechanisms, and P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) (ABCG2).

methodsThe pharmacokinetic effects of substrates or inhibitors of CYP3A4, P-gp and Bcrp (ABCG2) on rivaroxaban were studied in healthy volunteers.

resultsRivaroxaban did not interact with midazolam (CYP3A4 probe substrate). Exposure to rivaroxaban when co-administered with midazolam was slightly decreased by 11% (95% confidence interval [CI] -28%, 7%) compared with rivaroxaban alone. The following drugs moderately affected rivaroxaban exposure, but not to a clinically relevant extent: erythromycin (moderate CYP3A4/P-gp inhibitor; 34% increase [95% CI 23%, 46%]), clarithromycin (strong CYP3A4/moderate P-gp inhibitor; 54% increase [95% CI 44%, 64%]) and fluconazole (moderate CYP3A4, possible Bcrp [ABCG2] inhibitor; 42% increase [95% CI 29%, 56%]). A significant increase in rivaroxaban exposure was demonstrated with the strong CYP3A4, P-gp/Bcrp (ABCG2) inhibitors (and potential CYP2J2 inhibitors) ketoconazole (158% increase [95% CI 136%, 182%] for a 400 mg once daily dose) and ritonavir (153% increase [95% CI 134%, 174%]).

conclusionsResults suggest that rivaroxaban may be co-administered with CYP3A4 and/or P-gp substrates/moderate inhibitors, but not with strong combined CYP3A4, P-gp and Bcrp (ABCG2) inhibitors (mainly comprising azole-antimycotics, apart from fluconazole, and HIV protease inhibitors), which are multi-pathway inhibitors of rivaroxaban clearance and elimination.

Indexed as

AdolescentAdultAnticoagulantsATP Binding Cassette Transporter, Subfamily B, Member 1ClarithromycinCytochrome P-450 CYP2J2Cytochrome P-450 CYP3ACytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemDrug InteractionsEnzyme InhibitorsErythromycinHumansKetoconazoleMetabolic Clearance RateMidazolamAnticoagulantsATP Binding Cassette Transporter, Subfamily B, Member 1ClarithromycinCYP2J2 protein, humanCYP3A4 protein, humanCytochrome P-450 CYP2J2Cytochrome P-450 CYP3ACytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemEnzyme InhibitorsErythromycinKetoconazoleMidazolamMorpholinesRivaroxabanThiophenescytochrome P450drug interactionshealthy subjectsP-glycoproteinrivaroxaban

Identifiers

PMID23305158
PMCPMC3769672
OpenAlexW1564607482

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.