title: Clarithromycin, trimethoprim, and penicillin and oxidative nucleic acid modifications in humans: randomised, controlled trials.
abstract: In 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.
  
  
  
  This 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.
  
  
  
  Clarithromycin 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.
  
  
  
  Clarithromycin 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.
authors.affiliation: Laboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Pharmacology, Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Emil List
authors.initials: EL
authors.lastname: Larsen
authors.affiliation: Laboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Pharmacology, Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Vanja
authors.initials: V
authors.lastname: Cejvanovic
authors.affiliation: Laboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Pharmacology, Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Laura Kofoed
authors.initials: LK
authors.lastname: Kjaer
authors.affiliation: Laboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten Thorup
authors.initials: MT
authors.lastname: Pedersen
authors.affiliation: Laboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sara Daugaard
authors.initials: SD
authors.lastname: Popik
authors.affiliation: Laboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lina Kallehave
authors.initials: LK
authors.lastname: Hansen
authors.affiliation: Department of Clinical Pharmacology, Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jon Traerup
authors.initials: JT
authors.lastname: Andersen
authors.affiliation: Department of Clinical Pharmacology, Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Espen
authors.initials: E
authors.lastname: Jimenez-Solem
authors.affiliation: Laboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kasper
authors.initials: K
authors.lastname: Broedbaek
authors.affiliation: Laboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Petersen
authors.affiliation: Laboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Pharmacology, Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Weimann
authors.affiliation: Laboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Pharmacology, Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Henriksen
authors.affiliation: Section of Experimental Animal Models, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
authors.affiliation: Institute of Health, Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.affiliation: Laboratory of Clinical Pharmacology (Q7642), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Pharmacology, Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Henrik Enghusen
authors.initials: HE
authors.lastname: Poulsen
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000652:urine; D017291:Clarithromycin / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D006151:Guanosine / Q000031:analogs & derivatives / Q000652:urine; D064368:Healthy Volunteers; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010404:Penicillin V / Q000494:pharmacology; D010919:Placebos; D012313:RNA / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014295:Trimethoprim / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D010919:Placebos; D017382:Reactive Oxygen Species; D006151:Guanosine; C046215:8-hydroxyguanosine; D008315:Malondialdehyde; D012313:RNA; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D014295:Trimethoprim; D003849:Deoxyguanosine; D017291:Clarithromycin; D010404:Penicillin V
keywords: 8-oxo-7,8-dihydro-2′-deoxyguanosine; 8-oxo-7,8-dihydroguanosine; DNA oxidation; RNA oxidation; antibiotics; oxidative stress