Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
J Pharm Sci. 2011 Sep;100(9):3560-76. doi: 10.1002/jps.22656. Epub 2011 Jun 7.
Many pathophysiological circumstances vary during 24 h periods. Many physiologic processes undergo biological rhythms, including the sleep-wake rhythm and metabolism. Disruptive effect in the 24 h variations can manifest as the emergence or exacerbation of pathological conditions. So, chronotherapeutics is gaining increasing interest in experimental biology, medicine, pharmacy, and drug delivery. This science and the plethora of information should be used intelligently for optimizing the effectiveness and safety of the drug, relying on the timing of drug intake. These chronopharmacological findings are affected by not only the pharmacodynamics but also pharmacokinetics of drugs. The mammalian circadian pacemaker is located in the suprachiasmatic nucleus. The molecular mechanisms are associated with Clock genes that control the circadian rhythms in physiology, pathology, and behavior. Clock controls several diseases such as metabolic syndrome, cancer, and so on. CLOCK mutation influences the expression of both rhythmic and nonrhythmic genes in wild-type tissues. These genotypic changes lead to phenotypic changes, affecting the drug pharmacokinetic and pharmacodynamic parameters. This review is intended to elaborate system regulating biological rhythms and the applicability in pharmaceutics from viewpoints of the intraindividual and interindividual variabilities of Clock genes.
许多病理生理情况在 24 小时内发生变化。许多生理过程都经历生物节律，包括睡眠-觉醒节律和代谢。24 小时变化的干扰作用可能表现为病理状况的出现或恶化。因此，时间治疗学在实验生物学、医学、药学和药物输送领域越来越受到关注。这门科学和大量信息应该被明智地利用，以优化药物的有效性和安全性，依靠药物摄入的时间。这些时间药理学发现不仅受到药物的药效学，还受到药物动力学的影响。哺乳动物的生物钟位于视交叉上核。分子机制与 Clock 基因有关，Clock 基因控制生理、病理和行为的昼夜节律。Clock 控制着几种疾病，如代谢综合征、癌症等。CLOCK 突变会影响野生型组织中节律和非节律基因的表达。这些基因型变化导致表型变化，影响药物的药代动力学和药效学参数。本文旨在从 Clock 基因的个体内和个体间变异性的角度，详细阐述生物钟对生物节律的调控及其在药剂学中的应用。
