当今精准医学面临的挑战之一就是将分子时钟对药物药代动力学、毒性和疗效的影响与个体化时间治疗相结合。过去十年中，在免疫治疗、抗癌化疗以及心血管、代谢、炎症和神经疾病常用药物中，通过恰当的给药时机，已经证实了药物耐受性和/或疗效的显著改善。实验与人体研究最近揭示了性别差异的昼夜节律药物反应。现今，专门的随机临床试验应该旨在为日常医疗实践提供个性化的昼夜节律定时建议，整合远程长期监测昼夜节律度量的创新技术，单时间点活检的分子时钟功能的统计预测，以及多尺度生物节律数学模型。重要的是，需要明确鉴定昼夜节律功能强大的患者，在个性化时间治疗中获益最大。相反，非昼夜节律适应患者可能从以昼夜节律为靶点的新兴药物类别中获益。《药理学和毒理学年度评论》第64卷的最终在线出版日期预计为2024年1月。请参阅http://www.annualreviews.org/page/journal/pubdates以获取修订后的估计日期。

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. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 64 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.