title: The CYTONOX trial.
abstract: BACKGROUND
  In Denmark, it is estimated that 3-5% of children are obese. Obesity is associated with pathophysiological alterations that may lead to alterations in the pharmacokinetics of drugs. In adults, obesity was found to influence important drug-metabolising enzyme pathways. The impact of obesity-related alterations on drug metabolism and its consequences for drug dosing remains largely unknown in both children and adults. An altered drug metabolism may contribute significantly to therapeutic failure or toxicity. The aim of this trial is to investigate the in vivo activity of CYP3A4, CYP2E1 and CYP1A2 substrates in obese versus non-obese children.
  
  
  METHODS
  The CYTONOX trial is an open-label explorative pharmacokinetic trial. We intend to include 50 obese and 50 non-obese children. The primary end points are: in vivo clearance of CYP3A4, CYP2E1 and CYP1A2 substrates, which will be defined by using well-tested probes; midazolam, chlorzoxazone and caffeine. Each of the probes will be administered as a single dose. Subsequently, blood and urine samples will be collected at pre-specified times.
  
  
  CONCLUSIONS
  The aim of the CYTONOX trial is to investigate the in vivo activity of CYP3A4, CYP2E1 and CYP1A2 in obese and non-obese children. The results are expected to be used in the future as a basis for drug dosing recommendations in obese children.
  
  
  BACKGROUND
  The study was funded by the Danish Regions' "Medicinpuljen". The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
  
  
  BACKGROUND
  EudraCT: 2014-004554-34.
authors.affiliation: christina.gade@regionh.dk.
authors.forename: Christina
authors.initials: C
authors.lastname: Gade
authors.forename: Gerd
authors.initials: G
authors.lastname: Mikus
authors.forename: Hanne Rolighed
authors.initials: HR
authors.lastname: Christensen
authors.forename: Kim Peder
authors.initials: KP
authors.lastname: Dalhoff
authors.forename: Jens-Christian
authors.initials: JC
authors.lastname: Holm
authors.forename: Helle
authors.initials: H
authors.lastname: Holst
mesh_terms: D000293:Adolescent; D002110:Caffeine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002648:Child; D002753:Chlorzoxazone / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002985:Clinical Protocols; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D003718:Denmark; D005260:Female; D006801:Humans; D008297:Male; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D063766:Pediatric Obesity / Q000378:metabolism*
chemical_list: D002110:Caffeine; D019392:Cytochrome P-450 CYP2E1; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D002753:Chlorzoxazone; D008874:Midazolam