Chronobiology and Implications for Pharmacology

Although it has been understood for several decades that the actions of drugs can vary markedly depending on the time of day of exposure, consideration of daily timing is too often neglected in pharmacological research. A hierarchy of nearly 24 h (i.e., circadian) clocks derived from a transcription-translation feedback loop in individual cells regulates nearly all aspects of physiology at the level of cells, organs, and the organism. To improve drug safety and efficacy, drug studies would benefit from incorporation of perspectives from circadian biology in their design. This chapter presents an overview of key principles of circadian organization in mammals. Examples of daily rhythmicity in drug absorption, distribution, metabolism, and elimination are provided as well as a framework for understanding circadian rhythms in pharmacodynamics. The chapter reviews practical considerations for assessing circadian rhythmicity in pre-clinical studies of drug action including the use of multiple light/dark cycles for animal housing and circular statistics for their efficient detection.