The Role of Clock Genes in Pharmacology

Author:

Paschos Georgios K.1,Baggs Julie E.1,Hogenesch John B.12,FitzGerald Garret A.1

Affiliation:

1. Department of Pharmacology, Institute for Translational Medicine and Therapeutics, and

2. Penn Genome Frontiers Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104;, , ,

Abstract

The physiology of a wide variety of organisms is organized according to periodic environmental changes imposed by the earth's rotation. This way, a large number of physiological processes present diurnal rhythms regulated by an internal timing system called the circadian clock. As part of the rhythmicity in physiology, drug efficacy and toxicity can vary with time. Studies over the past four decades present diurnal oscillations in drug absorption, distribution, metabolism, and excretion. On the other hand, diurnal variations in the availability and sensitivity of drug targets have been correlated with time-dependent changes in drug effectiveness. In this review, we provide evidence supporting the regulation of drug kinetics and dynamics by the circadian clock. We also use the examples of hypertension and cancer to show current achievements and challenges in chronopharmacology.

Publisher

Annual Reviews

Subject

Pharmacology,Toxicology

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