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Circadian rhythm in pharmacokinetics and its relevance to chronotherapy

机译：昼夜节律在药代动力学及其与计时疗法的相关性

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摘要

Dosing time accounts for a large variability in efficacy and/or toxicity for many drugs. Therefore, chronotherapy has been shown to effectively improve drug efficacy and to reduce drug toxicity. Circadian changes in pharmacokinetics and pharmacodynamics (drug target) are two essential sources of time-varying drug effects. Pharmacokinetics determines the drug and metabolite concentrations (exposure) in target tissues/organs, thereby impacting drug efficacy and toxicity. Pharmacokinetic processes are generally divided into drug absorption, distribution, metabolism and excretion (so-called "ADME"). Recent years of studies have revealed circadian (similar to 24 h) rhythms in ADME processes, and clarified the underlying mechanisms related to circadian clock regulation. Furthermore, there is accumulating evidence that circadian pharmacokinetics can be translated to chronotoxicity and chronoefficacy. In this article, we review circadian rhythms in pharmacokinetic behaviors along with the underlying mechanisms. We also discuss the correlations of circadian pharmacokinetics with chronotoxicity and chronoefficacy.
机译：给药时间占许多药物的疗效和/或毒性的大幅度。因此，已显示计时疗法以有效提高药物疗效和减少药物毒性。昼夜昼夜药代动力学和药效学（药物目标）的变化是两个必要的时变药物源的根源。药代动力学决定了靶组织/器官中的药物和代谢物浓度（暴露），从而影响药物疗效和毒性。药代动力学过程通常分为药物吸收，分布，代谢和排泄（所谓的“Adme”）。近年来的研究已经揭示了Adme进程中的昼夜节律（类似于24小时），并澄清了与昼夜节日调节相关的潜在机制。此外，积累了昼夜节律药代动力学的证据可以转化为计时性和计时性。在本文中，我们审查了药代动力学行为的昼夜节律以及潜在的机制。我们还讨论了昼夜节律药代动力学与计时性和计时曲线的相关性。

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