Center for Functional Genomics and Bio-chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana Ljubljana, Slovenia.
IUBMB Life. 2013 Jun;65(6):487-96. doi: 10.1002/iub.1160. Epub 2013 Apr 3.
The biochemical basis of the mammalian circadian clock can be described by transcriptional-translational feedback loops with a period of about 24 h. Crucial endogenous factors are under circadian control (i.e., body temperature, blood pressure, hormone secretion and metabolite levels). Also, drug metabolism, including phases I-III and the drug-responsive nuclear receptors, is controlled by the clock. Disturbances in circadian rhythm in humans can lead to pathologies, which is exemplified by increased cancer risk in long-term shift workers. On the other hand, best tolerability of drugs with minimum side effects can be achieved if the timing of drug treatment is synchronized with the patients' individual clock. The aim of this review is to underline the importance of accepting the individuals' endogenous clock which can contribute to personalized, patient-friendly optimization of drug therapies.
哺乳动物生物钟的生化基础可以用大约 24 小时的转录-翻译反馈环来描述。关键的内源性因素受昼夜节律控制（即体温、血压、激素分泌和代谢物水平）。此外，药物代谢，包括 I 期-III 期和药物反应性核受体，也受时钟控制。人类昼夜节律紊乱可导致疾病，长期轮班工作者癌症风险增加就是一个例证。另一方面，如果药物治疗的时间与患者的个体生物钟同步，那么可以以最小的副作用实现最佳的药物耐受性。本文综述的目的是强调接受个体内源性时钟的重要性，这有助于实现药物治疗的个体化和患者友好型优化。
