In mammals, a variety of biological processes are subject to daily oscillations, and some of these are controlled by self-sustained oscillation mechanism called circadian clock. The rhythmic oscillations are driven by transcriptional-translational feedback loop consisting of negative and positive regulators encoded from circadian clock genes. This molecular oscillator regulates 24-hour rhythms in output physiology through the periodic activation/repression of clock-controlled genes. Accumulating evidences have revealed that daily oscillation in the physiological functions also affect drug dispositions in laboratory rodents. However, it is difficult to predict the circadian change in the drug pharmacokinetics in a diurnal active human by using the data collected from nocturnal active rodents. This review presents an overview of regulation mechanism for circadian rhythms in the expression of drug metabolism enzymes and xenobiotic transporters, and also describes the importance of evaluation of the difference in the circadian machinery between diurnal and nocturnal animals to choose the most appropriate times of day for drug administration.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science