Evidence map›Paper›PMID 30830337›Full record

ArticleMetabolomics : Official journal of the Metabolomic Society2017

Targeted and global pharmacometabolomics in everolimus-based immunosuppression: association of co-medication and lysophosphatidylcholines with dose requirement.

Dorothea Lesche, Vilborg Sigurdardottir, Alexander B Leichtle, Christos T Nakas, Uwe Christians, Lars Englberger, Martin Fiedler, Carlo R Largiadèr, Paul Mohacsi, Johanna Sistonen

Abstract read
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In one paragraph

Article in Metabolomics : Official journal of the Metabolomic Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 44% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
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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

10 authors at 3 institutions in 3 countries.

Dorothea LescheUniversity Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Vilborg SigurdardottirDepartment of Cardiology, Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Alexander B LeichtleUniversity Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Christos T NakasUniversity Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Uwe ChristiansiC42 Clinical Research and Development, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Lars EnglbergerDepartment of Cardiovascular Surgery, Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Martin FiedlerUniversity Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Carlo R LargiadèrUniversity Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Paul MohacsiDepartment of Cardiovascular Surgery, Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. paul.mohacsi@insel.ch.
Johanna SistonenUniversity Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
University of Bern · CHUniversity Hospital of Bern · CHUniversity of Colorado Denver · US

Funding

In Vivo Assessment of Calcineurin Inhibitor Toxicity in ChildrenR01HD070511 · NICHD · UNIVERSITY OF COLORADO DENVER · PI CHRISTIANS, UWE, THURMAN, JOSHUA M · 2011 to 2015
$1.9M
NICHD NIH HHS R01 HD070511
6 · The paper itself

Abstract

introductionThe immunosuppressive therapy with everolimus (ERL) after heart transplantation is characterized by a narrow therapeutic window and a substantial variability in dose requirement. Factors explaining this variability are largely unknown.

objectivesOur aim was to evaluate factors affecting ERL metabolism and to identify novel metabolites associated with the individual ERL dose requirement to elucidate mechanisms underlying ERL dose response variability.

methodWe used liquid chromatography coupled with mass spectrometry for quantification of ERL metabolites in 41 heart transplant patients and evaluated the effect of clinical and genetic factors on ERL pharmacokinetics. Non-targeted plasma metabolic profiling by ultra-performance liquid chromatography and high resolution quadrupole-time-of-flight mass spectrometry was used to identify novel metabolites associated with ERL dose requirement.

resultsThe determination of ERL metabolites revealed differences in metabolite patterns that were independent from clinical or genetic factors. Whereas higher ERL dose requirement was associated with co-administration of sodium-mycophenolic acid and the CYP3A5 expressor genotype, lower dose was required for patients receiving vitamin K antagonists. Global metabolic profiling revealed several novel metabolites associated with ERL dose requirement. One of them was identified as lysophosphatidylcholine (lysoPC) (16:0/0:0). Subsequent targeted analysis revealed that high levels of several lysoPCs were significantly associated with higher ERL dose requirement.

conclusionFor the first time, this study describes distinct ERL metabolite patterns in heart transplant patients and detected potentially new drug-drug interactions. The global metabolic profiling facilitated the discovery of novel metabolites associated with ERL dose requirement that might represent new clinically valuable biomarkers to guide ERL therapy.

Indexed as

AdultAgedBiomarkersChromatography, High Pressure LiquidCytochrome P-450 CYP3ADose-Response Relationship, DrugDrug InteractionsDrug Therapy, CombinationEverolimusFemaleHeart TransplantationHumansImmune ToleranceImmunologic Deficiency SyndromesImmunosuppression TherapyImmunosuppressive AgentsBiomarkersCYP3A5 protein, humanCytochrome P-450 CYP3AEverolimusImmunosuppressive AgentsLysophosphatidylcholinesMycophenolic AcidDose requirementEverolimus metabolismHeart transplantationPharmacometabolomics

Identifiers

PMID30830337
OpenAlexW2770056250

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Registered trials

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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.