Concepts in chronopharmacology.

Circadian and other rhythmic changes in biological susceptibility and response of organisms to a large variety of physical and chemical agents including medications and foods are rather common phenomena. Time-related differences in drug effects depend upon endogenous circadian rhythms, which include metabolic pathways. In addition, chronopharmacology investigates drug effects on parameters (e.g. circadian period, peak time, amplitude, and adjusted mean) used to characterize biological rhythms. A better understanding of periodic and thus predictable changes in drug effects can be attained by consideration of complementary concepts: (a) The chronokinetics for a drug, i.e. dosing time-dependent and predictable (rhythmic) changes in parameters used to characterize the pharmacokinetics (or the bioavailability) of a drug, e.g. Cmax, tmax, AUC, and t1/2; (b) the chronesthesy, i.e. rhythmic changes in susceptibility of the target biosystem to this drug, including CR in pharmacodynamic processes; and (c) the chronergy, i.e. the drug-integrated overall effect. One of the aims of chronopharmacology refers to the use of a chronopharmacological approach to clinical treatment so as to enhance both effectiveness and tolerance of a drug by determining the best biological time for its administration.