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

Jul 20, 2010Advanced drug delivery reviews

Timing-based drug strategies and differences in internal biological clocks within and between individuals

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Circadian rhythms are linked to physiological processes and may impact disease conditions such as depression, diabetes, and cancer.

The circadian clock regulates essential functions like sleep, hormone levels, and appetite on a 24-hour cycle.
Perturbations in circadian rhythms are associated with various health issues, including metabolic syndrome and cancer.
Clock genes control a wide range of physiological rhythms and behaviors, influencing disease expression.
Mutations in the CLOCK gene can alter the expression of both rhythmic and non-rhythmic genes.
Variability in drug pharmacokinetics and pharmacodynamics may be influenced by both individual and time-related factors.
Understanding the role of clock genes could enhance the effectiveness of chronopharmacotherapy in clinical settings.

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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.

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

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