Evidence map›Paper›PMID 25881619›Full record

Trial reportThe Journal of antimicrobial chemotherapy2015

Lack of a significant pharmacokinetic interaction between maraviroc and tacrolimus in allogeneic HSCT recipients.

Alex Ganetsky, Todd A Miano, Mitchell E Hughes, Robert H Vonderheide, David L Porter, Ran Reshef

Open access · greenAbstract readClinical Trial, Phase IClinical Trial, Phase II
In one paragraph

Trial report in The Journal of antimicrobial chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact, top 94% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
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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

6 authors at 4 institutions in 1 country.

Alex GanetskyDepartment of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Todd A MianoCenter for Pharmacoepidemiology Research and Training, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Mitchell E HughesDepartment of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia, PA, USA Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USA.
Robert H VonderheideAbramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA Abramson Cancer Center and the Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
David L PorterAbramson Cancer Center and the Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Ran ReshefAbramson Cancer Center and the Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA ran.reshef@uphs.upenn.edu.
University of Pennsylvania · USCancer Research Institute · USHospital of the University of Pennsylvania · USUniversity of the Sciences · US

Funding

Clinical Pharmacoepidemiology Training ProgramT32GM075766 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Sean Hennessy, Charles Edward Leonard · 2006 to 2026
$8.4M
Clinical Importance of Drug-Drug InteractionsR01AG025152 · NIA · UNIVERSITY OF PENNSYLVANIA · PI HENNESSY, SEAN, LI, LANG · 2006 to 2021
$8.1M
Lymphocyte trafficking blockade in allogeneic stem-cell transplantationK23CA178202 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RESHEF, RAN · 2013 to 2015
$520k
NCI NIH HHS K23 CA178202NCI NIH HHS K23CA178202NIA NIH HHS R01 AG025152NIGMS NIH HHS T32 GM075766NIGMS NIH HHS T32GM075766
6 · The paper itself

Abstract

objectivesEmerging data suggest that the combination of tacrolimus and the CCR5 antagonist maraviroc, both cytochrome P450-3A4 substrates, may be effective in preventing graft-versus-host disease in patients undergoing allogeneic HSCT. This study evaluated whether a pharmacokinetic interaction exists between these agents.

methodsThe study included 36 allogeneic HSCT recipients who received maraviroc + tacrolimus and 43 recipients of tacrolimus alone. We used a difference-in-differences analysis to examine the change in the concentration/dose ratios of tacrolimus after the discontinuation of maraviroc. In addition, we analysed the concentrations and dose requirements of tacrolimus in the two groups.

resultsThere was no significant difference in tacrolimus concentration/dose ratios in patients receiving maraviroc + tacrolimus compared with tacrolimus alone. Upon discontinuation of maraviroc, the change in concentration/dose ratio was small and not significant relative to the control group, and the effect estimate was further attenuated after adjustment for confounders [-0.35 (ng/mL)/(mg/day); P = 0.46]. In addition, the change in mean tacrolimus dose after discontinuation of maraviroc was similar between the groups (0.12 mg/day; P = 0.56), as was the change in mean tacrolimus concentration (0.02 ng/mL; P = 0.97).

conclusionsOur findings do not support a significant inhibitory effect of maraviroc on the metabolism of tacrolimus. These data demonstrate that this drug combination is safe and imply that the protective effect of maraviroc against graft-versus-host disease was not mediated through an increase in tacrolimus concentrations. These findings are important for the design of clinical trials that evaluate maraviroc in combination with cytochrome P450-3A4 substrates.

Indexed as

Drug InteractionsHematopoietic Stem Cell TransplantationAdultAgedCyclohexanesFemaleGraft vs Host DiseaseHumansImmunologic FactorsMaleMaravirocMiddle AgedProspective StudiesTacrolimusTransplantation, HomologousTriazolesCyclohexanesImmunologic FactorsMaravirocTacrolimusTriazoleschemokine receptorsimmunosuppressionpharmacologytransplantation

Identifiers

PMID25881619
PMCPMC4472330
OpenAlexW2041632904

What OpenQuestion holds

Textmetadata
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.