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Trends Mol Med. 2016 May;22(5):430-45. doi: 10.1016/j.molmed.2016.03.004. Epub 2016 Apr 5.

Dosing-Time Makes the Poison: Circadian Regulation and Pharmacotherapy.

Author information

1
Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK; Warwick Systems Biology Centre, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK. Electronic address: r.dallmann@warwick.ac.uk.
2
Department of Pharmacology, Faculty of Pharmacy, Istanbul University, Beyazit-Istanbul, Turkey.
3
Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK; Warwick Systems Biology Centre, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK.

Abstract

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

PMID:
27066876
DOI:
10.1016/j.molmed.2016.03.004
[Indexed for MEDLINE]
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