Department of Pharmacology, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA.
Annu Rev Pharmacol Toxicol. 2010;50:187-214. doi: 10.1146/annurev.pharmtox.010909.105621.
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.
各种生物体的生理学根据地球自转带来的周期性环境变化进行组织。这样，许多生理过程呈现出由内部计时系统（称为生物钟）调节的昼夜节律。作为生理学节律的一部分，药物的疗效和毒性可能随时间而变化。过去四十年的研究表明，药物吸收、分布、代谢和排泄存在昼夜波动。另一方面，药物靶点的可用性和敏感性的昼夜变化与药物有效性的时间依赖性变化相关。在这篇综述中，我们提供了支持生物钟调节药物动力学和药效学的证据。我们还使用高血压和癌症的例子展示了时间治疗药理学的当前成就和挑战。
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