Evidence map›Paper›PMID 34705149›Full record

ArticleCardiovascular drugs and therapy2023

Model-Based Risk Prediction of Rivaroxaban with Amiodarone for Moderate Renal Impaired Elderly Population.

Ziteng Wang, Eleanor Jing Yi Cheong, Pipin Kojodjojo, Eric Chun Yong Chan

Abstract read
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In one paragraph

Article in Cardiovascular drugs and therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.6field-weighted citation impact, top 15% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 14 citations in OpenAlex.

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  8. Transporters in Regulatory Science: Notable Contributions from Dr. Giacomini in the Past Two Decades.Drug metabolism and disposition: the biological fate of chemicals · 2022
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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

4 authors at 1 institution in 1 country.

Ziteng WangDepartment of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore.
Eleanor Jing Yi CheongDepartment of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore.
Pipin KojodjojoDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore, 119228, Singapore.
Eric Chun Yong ChanDepartment of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore. phaccye@nus.edu.sg.ORCID 0000-0001-6107-9072
National University of Singapore · SG

Funding

PEPTIDE CHEMISTRY SECTIONZ01HL002019 · NHLBI · HEART, LUNG, AND BLOOD INSTITUTE · PI SHAMBUREK, R · 1985 to 1995
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national university heart centre singapore (nuhcs) cardiovascular research institute (cvri) - core fund NUHSRO/2019/082/Coresceptre cg seed grant NMRC/CG/M008/2017
6 · The paper itself

Abstract

purposeIncreased bleeding risk was found associated with concurrent prescription of rivaroxaban and amiodarone. We previously recommended dose adjustment for rivaroxaban utilizing a physiologically based pharmacokinetic (PBPK) modeling approach. Our subsequent in vitro studies discovered the pivotal involvement of human renal organic anion transporter 3 (hOAT3) in the renal secretion of rivaroxaban and the inhibitory potency of amiodarone. This study aimed to redefine the disease-drug-drug interactions (DDDI) between rivaroxaban and amiodarone and update the potential risks.

methodsProspective simulations were conducted with updated PBPK models of rivaroxaban and amiodarone incorporating hOAT3-related parameters.

resultsSimulations to recapitulate previously explored DDDI in renal impairment showed a higher bleeding tendency in all simulation scenarios after integrating hOAT3-mediated clearance into PBPK models. Further sensitivity analysis revealed that both hOAT3 dysfunction and age could affect the extent of DDDI, and age was shown to have a more pivotal role on rivaroxaban in vivo exposure. When amiodarone was prescribed along with our recommended dose reduction of rivaroxaban to 10 mg in moderate renal impaired elderly people, it could result in persistently higher rivaroxaban peak concentrations at a steady state. To better manage the increased bleeding risk among such a vulnerable population, a dose reduction of rivaroxaban to 2.5 mg twice daily resulted in its acceptable in vivo exposure.

conclusionClose monitoring of bleeding tendency is essential for elderly patients with moderate renal impairment receiving co-prescribed rivaroxaban and amiodarone. Further dose reduction is recommended for rivaroxaban to mitigate this specific DDDI risk.

Indexed as

AmiodaroneRenal InsufficiencyAgedHemorrhageHumansKidneyRivaroxabanAmiodaroneRivaroxabanAmiodaroneGeriatricsPhysiologically based pharmacokinetic modelRenal impairmentRivaroxaban

Identifiers

PMID34705149
OpenAlexW3209026597

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.