Concepts of Circadian Chronopharmacology

Circadian and other rhythmic changes in biological susceptibility and response of organisms to a large variety of physical as well as chemical agents including medications and foods are rather common phenomena. Modern chronopharmacology investigates drug effects (a) as a function of biological timing and (b) upon parameters characterizing the endogenous bioperiodicities. A better understanding of periodic and thus predictable changes in drug effects can be attained through consideration of complementary concepts: (1) the chronokinetics of a drug--dosing time-dependent and predictable (rhythmic) changes in parameters used to characterize the pharmacokinetics (or the bioavailability) of a drug, e.g., maximum concentration (Cmax), span of time to reach Cmax (tmax), area under the concentration-time curve (AUC), half-life (t1/2), etc.; (2) the chronesthesy (rhythmic changes in susceptibility of a target biosystem to this drug); and (3) the chronergy (the drug-integrated overall effects). One of the aims of chronopharmacology is solving problems of drug optimization. Chronotherapy refers to the use of a chronopharmacologic approach to clinical treatment so as to enhance both effectiveness and tolerance of a drug by determining the best biological time for its dosing.