Chronopharmacology based on molecular clock

Chronotherapy is especially relevant, when the risk and/or intensity of the symptoms of disease vary predicably over time as exemplified by allergic rhinitis, arthritis, asthma, myocardial infarction, congestive heart failure, stroke, and peptic ulcer disease. The effectiveness and toxicity of many drugs vary depending on dosing time. Such chronopharmacological phenomena are influenced by not only the pharmacodynamics but also pharmacokinetics of medications. One approach to increasing the efficiency of pharmacotherapy is administering drugs at times during which they are best tolerated. From viewpoints of pharmaceutics, the application of biological rhythm to pharmacotherapy may be accomplished by the appropriate timing of conventionally formulated tabletes and capsules, and the special drug delivery system to synchronize drug concentrations to rhythms in disease activity. In all living organisms, one of the most indispensable biological functions is the circadian clock (suprachiasmatic nucleus; SCN), which acts like a multifunction timer to regulate homeostatic systems such as sleep and activity, hormone levels, appetite, and other bodily functions with 24 hr cycles. Clock genes were identified as the genes that ultimately control a vast array of circadian rhythms in physiology and behavior. Clock gene regulates several disease such as cancer, metabolic syndrome and sleep etc. Therefore, we introduce an overview of the dosing time-dependent alterations in therapeutic outcome and safety of drug. The underlying mechanisms and usefulness are introduced from viewpoints of clock genes and the possibility of pharmacotherapy based on clock genes.