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Chronobiol Med > Volume 5(1); 2023 > Article
Lee: Importance of Circadian Rhythm in Drug Administration Timing
Chronobiology plays a significant role in comprehending and managing both psychiatric disorders, such as mood and eating disorders [1,2], and physical illnesses, such as hypertension and Parkinson’s disease [3-5]. By recognizing the disruptions in circadian rhythms associated with these conditions, chronobiological interventions, such as timed medication administration, light therapy, and lifestyle modifications, can be applied to improve treatment outcomes. The impact of circadian rhythms on various bodily functions presents a challenge in determining the most suitable timing and dosage for drug administration, solely relying on the drug’s half-life without accounting for these rhythms. Regrettably, circadian rhythms are frequently overlooked when determining the appropriate timing for drug administration, highlighting the need for increased attention to the influence of circadian rhythms in pharmacotherapy.
Chronopharmacology is an interdisciplinary field that unites pharmacology and chronobiology, the study of biological rhythms, to investigate the correlation between biological rhythms and the effectiveness and potential toxicity of drugs. This field acknowledges the impact of biological processes, including circadian rhythms, on drug metabolism, elimination, and treatment efficacy for specific medical conditions.
In clinical situations, the principles of chronopharmacology are critical for optimizing drug therapy for patients. The timing of drug administration can greatly impact the effectiveness and safety of drugs. For instance, some drugs may be more effective when administered at certain times of day, while others may have increased side effects or toxicity at different times. This highlights the importance of considering the patient’s circadian rhythms and sleep patterns when administering medications.
Moreover, chronopharmacology helps healthcare providers to tailor drug therapy to the individual needs of their patients. Individuals may have different circadian rhythms or sleep patterns, which can affect the way they metabolize medications. By taking these factors into account, healthcare providers can improve the safety and efficacy of drug therapy.
In a study in mice, the dosing time-dependent activity of four antidepressants was tested. Antidepressants with different modes of action differ in terms of their chronopharmacological profiles. Fluoxetine, venlafaxine, imipramine, and bupropion showed maximal antidepressant activity in the morning, afternoon, afternoon, and pre-dawn, respectively. These results suggest that therapeutic efficacy could be improved by drug dosing time and combinations. For example, treatment with fluoxetine in the morning and venlafaxine in the afternoon might maximize drug efficacy [6].
The study explored the use of chronotherapy, a drug intervention administered at specific times of the day to optimize efficacy and minimize adverse effects, in hematologic malignancy, specifically in lymphoma patients. The study used two cohorts of patients and found that administering the drug regimen in the afternoon improved survival and reduced toxicity, especially in female patients [7].
Chronopharmacology is a relatively new field of study that explores the relationship between the timing of drug administration and its effects on the human body. While there has been promising research in this field, there are also limitations to consider. One limitation of chronopharmacology is that there is a lack of standardization in terms of measuring circadian rhythms and determining the optimal time for drug administration. This makes it difficult to compare studies and draw definitive conclusions about the effectiveness of chronotherapy.
Another limitation is that the optimal timing of drug administration may vary depending on individual differences, such as age, sex, and genetics. This means that a one-size-fits-all approach to chronotherapy may not be effective, and personalized medicine may be necessary.
Despite these limitations, the field of chronopharmacology holds great promise for improving the effectiveness and safety of drug therapies. Further research in this field could lead to the development of more personalized treatment regimens that take into account individual circadian rhythms and other factors that influence drug metabolism and effectiveness. In addition, chronopharmacology may have applications beyond cancer treatment, including in the treatment of psychiatric disorders and other medical conditions.


Funding Statement

This study was supported by the Korea Health 21 R&D Project funded by the National Research Foundation of Korea (2019R1A2C2084158).

Conflicts of Interest

The author has no potential conflicts of interest to disclose.


1. Lee HJ. Circadian misalignment and bipolar disorder. Chronobiol Med 2019;1:132–136.
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2. Kim S, Lee HJ. Sleep and circadian rhythm disturbances in eating disorders. Chronobiol Med 2020;2:141–147.
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3. Douma LG, Gumz ML. Circadian clock-mediated regulation of blood pressure. Free Radic Biol Med 2018;119:108–114.
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4. Hwang Y. Circadian rhythms in Parkinson’s disease. Chronobiol Med 2022;4:137–140.
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5. Lee HJ. Unraveling the significance of circadian rhythms for health. Chronobiol Med 2022;4:93–94.
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6. Kawai H, Iwadate R, Ishibashi T, Kudo N, Kawashima Y, Mitsumoto A. Antidepressants with different mechanisms of action show different chronopharmacological profiles in the tail suspension test in mice. Chronobiol Int 2019;36:1194–1207.
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7. Kim DW, Byun JM, Lee JO, Kim JK, Koh Y. Chemotherapy delivery time affects treatment outcomes of female patients with diffuse large B cell lymphoma. JCI Insight 2023;8:e164767.
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