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      Chronopharmacological strategies: Intra- and inter-individual variability of molecular clock☆

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      Advanced Drug Delivery Reviews
      Elsevier BV

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          Abstract

          In all living organisms, one of the most indispensable biological functions is the circadian clock (suprachiasmatic nuclei; SCN), which acts like a multifunction timer to regulate homeostatic systems such as sleep and activity, hormone levels, appetite, and other bodily functions with 24h cycles. Circadian rhythms regulate diverse physiologic processes, including homeostatic functions of steroid hormones and their receptors. Perturbations of these rhythms are associated with pathogenic conditions such as depression, diabetes and cancer. Clock genes are identified as the genes that ultimately control a vast array of circadian rhythms in physiology and behavior. Clock gene regulates several diseases such as cancer, metabolic syndrome and sleep etc. CLOCK mutation affects the expression of rhythmic genes in wild-type (WT) tissue, but also affects that of non-rhythmic genes. On the other hand, the change of the drug pharmacodynamic and pharmacokinetic (PK/PD) parameters are influenced by not only inter-individual variability but also intra-individual variabilities 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 viewpoint of clock genes. On the other hand, several drugs have an effect on molecular clock. Thus, the knowledge of intra- and inter-individual variability of molecular clock should be applied for the clinical practice. Therefore, we introduce the regulatory system of biological rhythm from viewpoints of clock genes and the possibility of pharmacotherapy based on the intra- and inter-individual variability of clock genes. 2010 Elsevier B.V. All rights reserved.

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          Author and article information

          Journal
          Advanced Drug Delivery Reviews
          Advanced Drug Delivery Reviews
          Elsevier BV
          0169409X
          July 31 2010
          July 31 2010
          : 62
          : 9-10
          : 885-897
          Article
          10.1016/j.addr.2010.04.005
          20638941
          488b4d9d-76c0-4d3a-89aa-b2105925666f
          © 2010

          https://www.elsevier.com/tdm/userlicense/1.0/

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