了解昼夜动态:当前的进展和药物发现中时生物学的未来方向
Meltem Weger1, Benjamin D Weger1, Frédéric Gachon1
1Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia.
Expert opinion on drug discovery
|June 10, 2023
概括
药物的疗效和毒性取决于服用时间,由昼夜时钟控制. 在药物发现的早期纳入时代药理学可以改善治疗结果.
科学领域:
- 时间药理学 时间药理学
- 循环节律 循环节律 循环节律
- 药物新陈代谢 药物新陈代谢
背景情况:
- 哺乳动物生理学,包括药物代谢和运输,由昼夜时钟调节.
- 药物的疗效和毒性受到药物使用时间的显著影响.
研究的目的:
- 审查当前关于药物代谢的知识,以每日时间为依赖.
- 突出时间药理学策略在药物开发中的重要性.
- 讨论影响节律性药理动学的因素,这些因素在慢性药理学中经常被忽视.
主要方法:
- 关于时间药理学和昼夜节律的文献综述.
- 分析参与节奏药物代谢的分子机制和功能.
- 讨论影响因素,如性别,疾病,食和微生物群.
主要成果:
- 循环时钟调节药物运输和新陈代谢,影响药物的疗效和毒性.
- 诸如性别,代谢疾病,食和微生物群等因素会影响节律性药物药理动力学.
- 时间调节治疗显示出希望,特别是在癌症治疗中.
结论:
- 将时间药理学纳入临床前药物发现是成功临床转换的关键.
- 考虑昼夜节律和影响因素可以优化药物开发.
- 尽管有成本,但早期实施时间药理学具有显著的潜力.
相关概念视频
Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response
93
Circadian rhythms are cyclic changes that are crucial in plasma drug concentrations. Various standard circadian parameters, including core body temperature, heart rate, and other cardiovascular factors, directly impact disease states and the therapeutic response to drug therapy.
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
93
Circadian Rhythms and Gene Regulation
4.1K
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.1K
Chronopharmacokinetics: Time-Dependent Pharmacokinetics
171
Chronopharmacokinetics studies the temporal change in drug absorption and elimination. These changes can be cyclical or non-cyclical. Cyclical changes occur over a regular interval, while non-cyclical changes occur over a longer, irregular period.
Time-dependent pharmacokinetics refers to non-cyclical changes in drug rate processes over a period of time. It can lead to nonlinear pharmacokinetics, where the relationship between drug concentration and time is not proportional. Non-cyclical...
Time-dependent pharmacokinetics refers to non-cyclical changes in drug rate processes over a period of time. It can lead to nonlinear pharmacokinetics, where the relationship between drug concentration and time is not proportional. Non-cyclical...
171
Drug Discovery: Overview
8.1K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
8.1K
Factors Affecting Drug Biotransformation: Biological
188
Biological factors significantly impact drug metabolism, influencing drug clearance, efficacy, and potential toxicity.
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
188
Biological Clocks and Seasonal Responses
34.8K
The circadian—or biological—clock is an intrinsic, timekeeping, molecular mechanism that allows plants to coordinate physiological activities over 24-hour cycles called circadian rhythms. Photoperiodism is a collective term for the biological responses of plants to variations in the relative lengths of dark and light periods. The period of light-exposure is called the photoperiod.
34.8K


