Understanding circadian dynamics: current progress and future directions for chronobiology in drug discovery.

INTRODUCTION:Most mammalian physiology is orchestrated by the circadian clock, including drug transport and metabolism. As a result, efficacy and toxicity of many drugs are influenced by the timing of their administration, which has led to the establishment of the field of chronopharmacology. AREAS COVERED:In this review, the authors provide an overview of the current knowledge about the time-of-day dependent aspects of drug metabolism and the importance of chronopharmacological strategies for drug development. They also discuss the factors influencing rhythmic drug pharmacokinetic including sex, metabolic diseases, feeding rhythms, and microbiota, that are often overlooked in the context of chronopharmacology. This article summarizes the involved molecular mechanisms and functions and explains why these parameters should be considered in the process of drug discovery. EXPERT OPINION:Although chronomodulated treatments have shown promising results, particularly for cancer, the practice is still underdeveloped due to the associated high cost and time investments. However, implementing this strategy at the preclinical stage could offer a new opportunity to translate preclinical discoveries into successful clinical treatments.