Circadian rhythm in pharmacokinetics and its relevance to chronotherapy

Dong, Dong; Yang, Deguang; Lin, Luomin; Wang, Shuai; Wu, Baojian

doi:10.1016/j.bcp.2020.114045

Cited by 80 publications

(57 citation statements)

References 113 publications

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“…Enzymes involved in phase two metabolism including glutathione S-transferase, carboxylesterase, cysteine dioxygenase, UDP glucuronosyltransferase, and sulfotransferase are also expressed in a circadian manner [98]. The diverse roles, drug substrates, and site(s) of expression of such circadian-driven metabolizing enzymes have been the subject of recent and extensive review [99]. Rapid advances in molecular biology techniques [e.g., molecular cloning, gene editing, and chromatin immunoprecipitation (ChIP) analysis] have revealed both direct and indirect mechanisms of core clock gene regulation of circadian drug metabolizing enzyme transcription.…”

Section: Metabolismmentioning

confidence: 99%

Circadian rhythms: influence on physiology, pharmacology, and therapeutic interventions

Ayyar

Sukumaran

2021

J Pharmacokinet Pharmacodyn

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Circadian rhythms are ubiquitous phenomena that recur daily in a self-sustaining, entrainable, and oscillatory manner, and orchestrate a wide range of molecular, physiological, and behavioral processes. Circadian clocks are comprised of a hierarchical network of central and peripheral clocks that generate, sustain, and synchronize the circadian rhythms. The functioning of the peripheral clock is regulated by signals from autonomic innervation (from the central clock), endocrine networks, feeding, and other external cues. The critical role played by circadian rhythms in maintaining both systemic and tissue-level homeostasis is well established, and disruption of the rhythm has direct consequence for human health, disorders, and diseases. Circadian oscillations in both pharmacokinetics and pharmacodynamic processes are known to affect efficacy and toxicity of several therapeutic agents. A variety of modeling approaches ranging from empirical to more complex systems modeling approaches have been applied to characterize circadian biology and its influence on drug actions, optimize time of dosing, and identify opportunities for pharmacological modulation of the clock mechanisms and their downstream effects. In this review, we summarize current understanding of circadian rhythms and its influence on physiology, pharmacology, and therapeutic interventions, and discuss the role of chronopharmacometrics in gaining new insights into circadian rhythms and its applications in chronopharmacology.

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Section: Metabolismmentioning

confidence: 99%

Circadian rhythms: influence on physiology, pharmacology, and therapeutic interventions

Ayyar

Sukumaran

2021

J Pharmacokinet Pharmacodyn

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“…Whether oral or parenteral, absorption kinetics often depend on the physiological processes of administration, which in turn are regulated in a temporal manner. Key transporters are expressed in a way that makes their levels peak at specific times during the day ( 44 ); as a result, critical PK parameters such as C max , τ max , AUC, and Cl (which define the maximum drug concentration, the time needed to reach that concentration, the area under the curve of the drug, and the clearance rate, respectively) depend strongly on the time of day of administration ( 45 ). For example, a recent study of asthmatic children dosed with theophylline at either 06:00 or 21:00 showed twofold-higher serum levels of the drug when dosed at 21:00.…”

Section: Rhythms Of Homeostasis and Therapeuticsmentioning

confidence: 99%

Circadian Effects of Drug Responses

Nahmias

Androulakis

2021

Annu. Rev. Biomed. Eng.

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Circadian rhythms describe physiological systems that repeat themselves with a cycle of approximately 24 h. Our understanding of the cellular and molecular origins of these oscillations has improved dramatically, allowing us to appreciate the significant role these oscillations play in maintaining physiological homeostasis. Circadian rhythms allow living organisms to predict and efficiently respond to a dynamically changing environment, set by repetitive day/night cycles. Since circadian rhythms underlie almost every aspect of human physiology, it is unsurprising that they also influence the response of a living organism to disease, stress, and therapeutics. Therefore, not only do the mechanisms that maintain health and disrupt homeostasis depend on our internal circadian clock, but also the way drugs are perceived and function depends on these physiological rhythms. We present a holistic view of the therapeutic process, discussing components such as disease state, pharmacokinetics, and pharmacodynamics, as well as adverse reactions that are critically affected by circadian rhythms. We outline challenges and opportunities in moving toward personalized medicine approaches that explore and capitalize on circadian rhythms for the benefit of the patient. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 23 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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“…Recognition of the importance of these circadian clocks with regard to the best time for delivery of medications has created a field of medicine known as chronotherapy, where drugs are given at the correct circadian time to effect the best possible response and lowest toxicity. [19] This may also have relevance to continuous v. daytime feeding in the ICU. [20] There are many disruptors of circadian rhythms and sleep (i.e.…”

Section: Melatonin Sleep and The Icumentioning

confidence: 99%

Is there a role for melatonin in the intensive care unit?

Richards

Bentley

Gopalan

et al. 2021

South Afr J Crit Care

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In the last decade, there have been significant developments in the understanding of the hormone melatonin in terms of its physiology, regulatory role and potential utility in various domains of clinical medicine. Melatonin's purported properties include, among others, regulation of mitochondrial function, anti-inflammatory, anti-oxidative and neuro-protective effects, sleep promotion and immune enhancement. As such, its role has been explored specifically in the critical care setting in terms of many of these properties. This review addresses the physiological basis for considering melatonin in the critical care setting as well as the current evidence pertaining to its potential utility.

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Circadian rhythm in pharmacokinetics and its relevance to chronotherapy

Cited by 80 publications

References 113 publications

Circadian rhythms: influence on physiology, pharmacology, and therapeutic interventions

Circadian rhythms: influence on physiology, pharmacology, and therapeutic interventions

Circadian Effects of Drug Responses

Is there a role for melatonin in the intensive care unit?

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