Chrono-Pharmaceutical Approaches to Optimize Dosing Regimens Based on the Circadian Clock Machinery

Nov 1, 2021Biological & pharmaceutical bulletin

Using the Body’s Internal Clock to Improve Medicine Timing and Doses

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Daily rhythmic variations in biological functions may affect drug efficacy and toxicity.

The circadian clock regulates metabolism, physiology, and behavior in mammals over a 24-hour cycle.
Genetic studies indicate that components of the circadian clock influence the expression of drug sensitivity and disposition genes.
Chrono-pharmaceutical applications could optimize drug administration timing to enhance therapeutic effectiveness and reduce toxicity.
Pathological conditions may also show significant changes in symptom intensity based on the time of day.
Understanding circadian differences between diurnal and nocturnal animals is crucial for determining optimal drug administration times in humans.

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Daily rhythmic variations in biological functions affect the efficacy and/or toxicity of drugs: a large number of drugs cannot be expected to exhibit the same potency at different administration times. The "circadian clock" is an endogenous timing system that broadly regulates metabolism, physiology and behavior. In mammals, this clock governs the oscillatory expression of the majority of genes with a period length of approximately 24 h. Genetic studies have revealed that molecular components of the circadian clock regulate the expression of genes responsible for the sensitivity to drugs and their disposition. The circadian control of pharmacodynamics and pharmacokinetics enables 'chrono-pharmaceutical' applications, namely drug administration at appropriate times of day to optimize the therapeutic index (efficacy vs. toxicity). On the other hand, a variety of pathological conditions also exhibit marked day-night changes in symptom intensity. Currently, novel therapeutic approaches are facilitated by the development of chemical compound targeted to key proteins that cause circadian exacerbation of disease events. This review presents an overview of the current understanding of the role of the circadian biological clock in regulating drug efficacy and disease conditions, and also describes the importance of identifying the difference in the circadian machinery between diurnal and nocturnal animals to select the most appropriate times of day to administer drugs in humans.

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Chrono-Pharmaceutical Approaches to Optimize Dosing Regimens Based on the Circadian Clock Machinery

Abstract

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