Dosing-Time Makes the Poison: Circadian Regulation and Pharmacotherapy

Trends Mol Med. 2016 May;22(5):430-445. doi: 10.1016/j.molmed.2016.03.004. Epub 2016 Apr 5.


Daily rhythms in physiology significantly modulate drug pharmacokinetics and pharmacodynamics according to the time-of-day, a finding that has led to the concept of chronopharmacology. The importance of biological clocks for xenobiotic metabolism has gained increased attention with the discovery of the molecular circadian clockwork. Mechanistic understanding of the cell-autonomous molecular circadian oscillator and the circadian timing system as a whole has opened new conceptual and methodological lines of investigation to understand first, the clock's impact on a specific drug's daily variations or the effects/side effects of environmental substances, and second, how clock-controlled pathways are coordinated within a given tissue or organism. Today, there is an increased understanding of the circadian modulation of drug effects. Moreover, several molecular strategies are being developed to treat disease-dependent and drug-induced clock disruptions in humans.

Keywords: chronotherapy; chronotoxicity; circadian clocks; drug metabolism; pharmacotherapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Clocks
  • Chronopharmacokinetics
  • Circadian Clocks*
  • Circadian Rhythm
  • Drug Chronotherapy*
  • Drug-Related Side Effects and Adverse Reactions*
  • Humans
  • Pharmaceutical Preparations / administration & dosage*
  • Pharmaceutical Preparations / metabolism*
  • Xenobiotics / metabolism*
  • Xenobiotics / toxicity*


  • Pharmaceutical Preparations
  • Xenobiotics