The Role of Clock Genes in Pharmacology

被引:70
作者
Paschos, Georgios K. [1 ]
Baggs, Julie E. [1 ]
Hogenesch, John B. [1 ,2 ]
FitzGerald, Garret A. [1 ]
机构
[1] Univ Penn, Sch Med, Dept Pharmacol, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Penn Genome Frontiers Inst, Philadelphia, PA 19104 USA
关键词
circadian clock; chronopharmacology; blood pressure; cancer; drug; timing; AMBULATORY BLOOD-PRESSURE; NIGHT-SHIFT WORK; CONTINUOUS VENOUS INFUSION; CHRONIC JET-LAG; CIRCADIAN VARIATION; TEMPORAL VARIATIONS; COLORECTAL-CANCER; BREAST-CANCER; FOLINIC ACID; CHRONOMODULATED CHEMOTHERAPY;
D O I
10.1146/annurev.pharmtox.010909.105621
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:187 / 214
页数:28
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