Chronopharmacology and chronotherapeutics: definitions and concepts

Most knowledge of medications has been derived from single- and multiple-dose investigations in which pharmacokinetic and pharmacodynamic phenomena have been evaluated following one, usually, daytime drug administration. Chronopharmacologic studies involving the evaluation of such phenomena after each of several different clock-hour treatments during the day- and nighttime reveal that biological rhythmic processes, such as those of 24 hr, can profoundly affect the kinetics and effects of various medications. Several new concepts have arisen based on findings from chronopharmacologic investigations, such as chronokinetics, chronesthesy and chronergy. These are defined and discussed herein using illustrative examples. A major goal of chronopharmacologic research is to devise chronotherapeutic interventions. Chronotherapeutics is the optimization of drug effects and/or minimization of toxicity by timing medications with regard to biological rhythms. Chronotherapeutics takes into account predictable administration-time-dependent variation in the pharmacokinetics of drugs as well as the susceptibility of target tissues due to temporal organization of physiochemical processes and functions of the body as circadian and other rhythms. The unequally divided and once-daily theophylline treatment schedules for the clinical management of nocturnal asthma, which are discussed in this issue, represent steps toward a chronotherapy.