Chronopharmacology : new insights and therapeutic implications

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Abstract

Most facets of mammalian physiology and behavior vary according to time-of-day thanks to an endogenous “circadian” clock. Therefore, it is not surprising that many aspects of pharmacology and toxicology also oscillate according to the same 24-hour 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, but organized in hierarchical fashion. Interestingly, some aspects of physiology and behavior are controlled directly via a “master clock” in the suprachiasmatic nuclei of the hypothalamus, while 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 considering “chrono-interactions” among different clock-regulated systems.

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