The role of clock genes in pharmacology.
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.
Paschos
Georgios K
GK
Department of Pharmacology, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA. gpaschos@mail.med.upenn.edu
Baggs
Julie E
JE
Hogenesch
John B
JB
FitzGerald
Garret A
GA
D056930:ARNTL Transcription Factors / Q000235:genetics; D000818:Animals; D001683:Biological Clocks / Q000235:genetics*; D001794:Blood Pressure; D056926:CLOCK Proteins / Q000235:genetics; D002940:Circadian Rhythm; D006152:Cyclic GMP / Q000096:biosynthesis; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy; D009569:Nitric Oxide / Q000096:biosynthesis; D010599:Pharmacokinetics; D010600:Pharmacology; D012084:Renin-Angiotensin System / Q000187:drug effects; D013493:Suprachiasmatic Nucleus / Q000502:physiology
D056930:ARNTL Transcription Factors; D009569:Nitric Oxide; D056926:CLOCK Proteins; D006152:Cyclic GMP