Ohdo Shigehiro
Clinical Pharmacokinetics, Division of Clinical Pharmacy, Department of Medico-Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Drug Metab Pharmacokinet. 2007 Feb 25;22(1):3-14. doi: 10.2133/dmpk.22.3.
The mammalians circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN) and influences a multitude of biological processes, including the sleep-wake rhythm. Clock genes are the genes that control the circadian rhythms in physiology and behavior. The effectiveness and toxicity of many drugs vary depending on dosing time associated with 24 hr rhythms of biochemical, physiological and behavioral processes under the control of circadian clock. Such chronopharmacological phenomena are influenced by not only the pharmacokinetics but also pharmacodynamics of medications. Identification of a rhythmic marker for selecting dosing time will lead to improved progress and diffusion of chronopharmacotherapy. The mechanisms underlying chronopharmacological findings should be clarified from the viewpoint of clock genes. On the other hand, several drugs have an effect on circadian clock. The knowledge of interactions between circadian clock and drugs should be very useful for clinical practice. Therefore, I introduce the regulatory system of biological rhythm from viewpoints of clock genes and the possibility of pharmacotherapy based on clock genes.
哺乳动物的昼夜节律起搏器位于成对的视交叉上核(SCN)中,并影响包括睡眠-觉醒节律在内的多种生物过程。时钟基因是控制生理和行为昼夜节律的基因。许多药物的有效性和毒性取决于给药时间,这与昼夜节律时钟控制下的生化、生理和行为过程的24小时节律相关。这种时辰药理学现象不仅受药物的药代动力学影响,还受药效学影响。识别用于选择给药时间的节律性标志物将有助于时辰药物治疗的改进和推广。应从时钟基因的角度阐明时辰药理学发现的潜在机制。另一方面,几种药物对昼夜节律时钟有影响。昼夜节律时钟与药物之间相互作用的知识对临床实践非常有用。因此,我将从时钟基因的角度介绍生物节律的调节系统以及基于时钟基因的药物治疗可能性。