title: The role of circadian timing system on drug metabolism and detoxification.
abstract: BACKGROUND
  It has been known for a long time that the efficiency and toxicity of drugs change during a 24-h period. However, the molecular mechanisms involved in these processes have started to emerge only recently.
  
  
  METHODS
  This review aims to highlight recent discoveries showing the direct role of the molecular circadian clock in xenobiotic metabolism at the transcriptional and post-transcriptional levels in the liver and intestine, and the different ways of elimination of these metabolized drugs via biliary and urine excretions. Most of the related literature focuses on transcriptional regulation by the circadian clock of xenobiotic metabolism in the liver; however, the role of this timing system in the excretion of metabolized drugs and the importance of the kidney in this phenomenon are generally neglected. The goal of this review is to describe the molecular mechanisms involved in rhythmic drug metabolism and excretion.
  
  
  CONCLUSIONS
  Chronopharmacology is used to analyze the metabolism of drugs in mammals according to the time of day. The circadian timing system plays a key role in the changes of toxicity of drugs by influencing their metabolisms in the liver and intestine in addition to their excretion via bile flow and urine.
authors.affiliation: University of Lausanne, Department of Pharmacology and Toxicology, CH-1005 Lausanne, Switzerland. Frederic.Gachon@unil.ch
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gachon
authors.forename: Dmitri
authors.initials: D
authors.lastname: Firsov
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D001659:Biliary Tract / Q000378:metabolism; D057906:Circadian Clocks; D002940:Circadian Rhythm / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D013997:Time Factors
chemical_list: D004364:Pharmaceutical Preparations