Musiek Erik S, Fitzgerald Garret A
Department of Neurology, Washington University School of Medicine, 7401 Byron Pl., Saint Louis, MO 63105, USA.
Handb Exp Pharmacol. 2013;217(217):243-60. doi: 10.1007/978-3-642-25950-0_10.
Circadian rhythms regulate a vast array of biological processes and play a fundamental role in mammalian physiology. As a result, considerable diurnal variation in the pharmacokinetics, efficacy, and side effect profiles of many therapeutics has been described. This variation has subsequently been tied to diurnal rhythms in absorption, distribution, metabolism, and excretion, as well as in pharmacodynamic variables, such as target expression. More recently, the molecular basis of circadian rhythmicity has been elucidated with the identification of clock genes, which oscillate in a circadian manner in most cells and tissues and regulate transcription of large sets of genes. Ongoing research efforts are beginning to reveal the critical role of circadian clock genes in the regulation of pharmacologic parameters, as well as the reciprocal impact of drugs on circadian clock function. This chapter will review the role of circadian clocks in the pharmacokinetics and pharmacodynamics of drug response and provide several examples of the complex regulation of pharmacologic systems by components of the molecular circadian clock.
昼夜节律调节着大量的生物过程，在哺乳动物生理学中发挥着重要作用。因此，许多治疗药物的药代动力学、疗效和副作用方面存在显著的昼夜变化已被描述。这种变化随后与吸收、分布、代谢、排泄以及药效学变量（如靶点表达）的昼夜节律相关联。最近，随着时钟基因的鉴定，昼夜节律的分子基础得以阐明，这些基因在大多数细胞和组织中以昼夜节律方式振荡，并调节大量基因的转录。正在进行的研究工作开始揭示昼夜节律时钟基因在调节药理学参数中的关键作用，以及药物对昼夜节律时钟功能的相互影响。本章将综述昼夜节律时钟在药物反应的药代动力学和药效学中的作用，并提供分子昼夜节律时钟组件对药理系统复杂调节的几个例子。
