Review: Chronopharmacology; A Biological Rhythm

Chronopharmacology is the study of how the effects of drugs vary with biological timing and endogenous periodicities. The goal is to improve our understanding of periodic and thus predictable (e.g. circadian) changes in both desired effects (chronoeffectiveness) and tolerance (chronotolerance) of medications. Dosing time-dependent changes also include quantification of parameters characterizing endogenous circadian rhythms (CR), in terms of pharmacologic effects, e.g. the 24-h adjusted mean (M), the period , the amplitude (A, the peak-to-trough difference), and the acrophase , the peak time location in the 24-h scale). Chronopharmacology became recognized as a scientific domain of investigation only in the early 1970s. For conventionally trained pharmacologists, it was not clear that predictable temporal variations of effects and disposition of agents (e.g. medications, hormones, and toxic substances) are governed by endogenous biological rhythms rather than by changes of external factors. On the 24-h scale (as well as on the yearly scale) there are peaks and troughs of physiological variables that are not randomly distributed; their respective locations correspond to a temporal organization controlled by a set of pacemakers (so-called biological clocks) became recognized as a scientific domain of investigation only in the early 1970s.