Because various physiological functions exhibit circadian rhythms, pharmacokinetics and/or pharmacodynamics of many medications show 24-hour rhythmicity. Therefore, optimization of the timing of drug administration, i.e., chronotherapy, is important to maximize therapeutic efficacy and/or minimize the adverse effects. Recently, we revealed that the dosing time of oral direct factor Xa inhibitors affects their efficacy in rats. However, their dosing time is not taken into account in clinical practice. In addition, various long-acting drugs, to which chronotherapy is not applicable, have recently been developed. Thus, it is time to reconsider the importance of chronotherapy.
Circadian rhythms are generated by the intracellular circadian clocks, and accumulating evidence has revealed that impairment of circadian clocks contributes to the development of lifestyle-related diseases. For example, we found that circadian clocks are disrupted in the peripheral tissues of both obese diabetic mice and diabetic patients and that this impairment precedes metabolic abnormalities. Moreover, we demonstrated that circadian clock in each tissue (liver and white and brown adipose tissues) play a role in glucose, lipid, and energy metabolism, respectively. These findings suggest that circadian clocks in the peripheral tissues are pharmacological targets for lifestyle-related diseases. Therefore, we are attempting to develop therapeutic agents for treating circadian clock disruption.