Development of New Chronopharmacotherapies Based on Biological Rhythm

Jan 4, 2003Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan

Developing new medicines that work with the body's natural daily rhythms

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Abstract

Interferon disrupts the rhythm of locomotor activity, body temperature, and clock gene expression in mammals.

The mammalian circadian pacemaker is located in the suprachiasmatic nuclei (SCN).
Clock genes manage circadian rhythms that influence physiology and behavior.
Drug effectiveness and toxicity may vary based on the timing of administration relative to circadian rhythms.
Monitoring rhythmic markers could aid in selecting optimal dosing times for medications.
Some drugs can negatively impact 24-hour rhythms, potentially leading to health issues.
Dosing schedules that minimize the adverse effects on clock function may enhance chronopharmacotherapy.

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The mammalian circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN). Clock genes are the genes that control the circadian rhythms of physiology and behavior. The effectiveness and toxicity of many drugs vary depending on dosing time associated with 24-h rhythms of biochemical, physiological, and behavioral processes under the control of the circadian clock. However, many drugs are still administered without regard to the time of day. Identification of a rhythmic marker for selecting dosing time will lead to improved progress and diffusion of chronopharmacotherapy. The monitoring of rhythmic markers may be useful in choosing the most appropriate time of day for administration of drugs and may increase their therapeutic effects and/or reduce their side effects. On the other hand, several drugs can cause alterations in 24-h rhythms, leading to illness and altered homeostatic regulation. Here, we show the disruptive effect of interferon on the rhythm of locomotor activity, body temperature, and clock gene mRNA expression in the periphery and SCN. The alteration of the clock function, a new concept of adverse effects, can be overcome by devising a dosing schedule that minimizes adverse drug effects on clock function. Furthermore, to produce new rhythmicity by manipulating the conditions of living organs using rhythmic administration of altered feeding schedules or several drugs appears to lead to the new concept of chronopharmacotherapy. One approach to increasing the efficiency of pharmacotherapy is administering drugs at times during which they are best effective and/or tolerated.

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Development of New Chronopharmacotherapies Based on Biological Rhythm

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