期刊
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 54
卷 54, 期 -, 页码 339-361出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-011613-135923
关键词
circadian rhythms; drug metabolism; chronotherapy; cancer; peripheral oscillators; systems biology
资金
- European Research Council [260988] Funding Source: Medline
- European Research Council (ERC) [260988] Funding Source: European Research Council (ERC)
Most facets of mammalian physiology and behavior vary according to time of day, thanks to endogenous circadian clocks. Therefore, it is not surprising that many aspects of pharmacology and toxicology also oscillate according to the same 24-h clocks. Daily oscillations in abundance of proteins necessary for either drug absorption or metabolism result in circadian pharmacokinetics, and oscillations in the physiological systems targeted by these drugs result in circadian pharmacodynamics. These clocks are present in most cells of the body, organized in a hierarchical fashion. Interestingly, some aspects of physiology and behavior are controlled directly via a master clock in the suprachiasmatic nuclei of the hypothalamus, whereas others are controlled by slave oscillators in separate brain regions or body tissues. Recent research shows that these clocks can respond to different cues and thereby show different phase relationships. Therefore, full prediction of chronopharmacology in pathological contexts will likely require a systems biology approach that considers chronointeractions among different clock-regulated systems.
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