Evidence map›Paper›PMID 28185274›Full record

Trial reportBritish journal of clinical pharmacology2017

Clarithromycin, trimethoprim, and penicillin and oxidative nucleic acid modifications in humans: randomised, controlled trials.

Emil List Larsen, Vanja Cejvanovic, Laura Kofoed Kjaer, Morten Thorup Pedersen, Sara Daugaard Popik, Lina Kallehave Hansen, Jon Traerup Andersen, Espen Jimenez-Solem, Kasper Broedbaek, Morten Petersen and 5 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in British journal of clinical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Article
  4. Review
  5. Article
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

15 authors.

Emil List LarsenLaboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Vanja CejvanovicLaboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Laura Kofoed KjaerLaboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Morten Thorup PedersenLaboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Sara Daugaard PopikLaboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Lina Kallehave HansenLaboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Jon Traerup AndersenDepartment of Clinical Pharmacology, Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.
Espen Jimenez-SolemDepartment of Clinical Pharmacology, Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.
Kasper BroedbaekLaboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Morten PetersenLaboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Allan WeimannLaboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Trine HenriksenLaboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Jens LykkesfeldtSection of Experimental Animal Models, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
Christian Torp-PedersenInstitute of Health, Science and Technology, Aalborg University, Aalborg, Denmark.
Henrik Enghusen PoulsenLaboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsIn vitro studies have demonstrated that formation of reactive oxygen species (ROS) contributes to the effect of bactericidal antibiotics. The formation of ROS is not restricted to bacteria, but also occurs in mammalian cells. Oxidative stress is linked to several diseases. This study investigates whether antibiotic drugs induce oxidative stress in healthy humans as a possible mechanism for adverse reactions to the antibiotic drugs.

methodsThis study contains information from two randomised, controlled trials. Participants underwent 1 week treatment with clarithromycin, trimethoprim, phenoxymethylpenicillin (penicillin V), or placebo. Oxidative modifications were measured as 24-h urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and plasma levels of malondialdehyde before and after treatment as a measurement of DNA oxidation, RNA oxidation, and lipid peroxidation, respectively.

resultsClarithromycin significantly increased urinary excretion of 8-oxodG by 22.0% (95% confidence interval (CI): 3.6-40.4%) and 8-oxoGuo by 14.9% (95% CI: 3.7-26.1%). Further, we demonstrated that trimethoprim significantly lowered urinary excretion of 8-oxodG by 21.7% (95% CI: 5.8-37.6%), but did not influence urinary excretion of 8-oxoGuo. Penicillin V did not influence urinary excretion of 8-oxodG or 8-oxoGuo. None of the antibiotic drugs influenced plasma levels of malondialdehyde.

conclusionClarithromycin significantly increases oxidative nucleic acid modifications. Increased oxidative modifications might explain some of clarithromycin's known adverse reactions. Trimethoprim significantly lowers DNA oxidation but not RNA oxidation. Penicillin V had no effect on oxidative nucleic acid modifications.

Indexed as

8-Hydroxy-2'-DeoxyguanosineAdultAnti-Bacterial AgentsBiomarkersClarithromycinDeoxyguanosineDNAGuanosineHealthy VolunteersHumansLipid PeroxidationMaleMalondialdehydeOxidation-ReductionOxidative StressPenicillin V8-Hydroxy-2'-Deoxyguanosine8-hydroxyguanosineAnti-Bacterial AgentsBiomarkersClarithromycinDeoxyguanosineDNAGuanosineMalondialdehydePenicillin VPlacebosReactive Oxygen SpeciesRNATrimethoprim8-oxo-7,8-dihydro-2′-deoxyguanosine8-oxo-7,8-dihydroguanosineantibioticsDNA oxidationoxidative stressRNA oxidation

Identifiers

PMID28185274
PMCPMC5510073

What OpenQuestion holds

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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.