Circadian Regulation of Drug Responses: Toward Sex-Specific and Personalized Chronotherapy.

IF 11.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-09-18 DOI:10.1146/annurev-pharmtox-051920-095416
Francis A Lévi, Alper Okyar, Eva Hadadi, Pasquale F Innominato, Annabelle Ballesta
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Abstract

Today's challenge for precision medicine involves the integration of the impact of molecular clocks on drug pharmacokinetics, toxicity, and efficacy toward personalized chronotherapy. Meaningful improvements of tolerability and/or efficacy of medications through proper administration timing have been confirmed over the past decade for immunotherapy and chemotherapy against cancer, as well as for commonly used pharmacological agents in cardiovascular, metabolic, inflammatory, and neurological conditions. Experimental and human studies have recently revealed sexually dimorphic circadian drug responses. Dedicated randomized clinical trials should now aim to issue personalized circadian timing recommendations for daily medical practice, integrating innovative technologies for remote longitudinal monitoring of circadian metrics, statistical prediction of molecular clock function from single-timepoint biopsies, and multiscale biorhythmic mathematical modelling. Importantly, chronofit patients with a robust circadian function, who would benefit most from personalized chronotherapy, need to be identified. Conversely, nonchronofit patients could benefit from the emerging pharmacological class of chronobiotics targeting the circadian clock.

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药物反应的昼夜节律调节:实现性别特异性和个性化的慢性疗法
如今,精准医学面临的挑战包括整合分子钟对药物药代动力学、毒性和疗效的影响,以实现个性化的时间疗法。在过去的十年中,通过合理安排用药时间,药物的耐受性和/或疗效得到了显著改善,这一点已在免疫疗法和癌症化疗以及心血管、代谢、炎症和神经系统疾病的常用药物治疗中得到证实。最近的实验和人体研究发现,昼夜节律药物反应具有性别双态性。现在,专门的随机临床试验应着眼于为日常医疗实践提供个性化的昼夜节律时间建议,将昼夜节律指标的远程纵向监测、从单时间点活检中对分子钟功能的统计预测以及多尺度生物节律数学建模等创新技术结合起来。重要的是,需要确定昼夜节律功能健全的 "昼夜节律适宜 "患者,他们将从个性化的 "昼夜节律疗法 "中获益最多。相反,非昼夜节律失调患者则可以从针对昼夜节律的新兴药理类慢性生物制剂中获益。
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来源期刊
CiteScore
27.80
自引率
0.00%
发文量
53
期刊介绍: Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.
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