New aspects of human chronopharmacology

Regular and thus predictable changes in biologic susceptibility and response to a large variety of physical as well as chemical agents can now be viewed as a rather common phenomenon. Chronopharmacology involves both the investigation of drug effects as a function of biologic timing and the investigation of drug effects upon rhythm characteristics. Illustrative examples of circadian chronopharmacolgy in man are discussed, keeping in mind that the objective demonstration of chronopharmacologic facts needs the use of an appropriate methodology. Circadian changes in the effects of various chemical agents have been documented: histamine, sodium salicylate, acetylcholine, halothane, prostaglandine F, reserpine, cyproheptadine, ethanol, insulin, chlorothiazide, oxymetholone, orciprenalin and SCH 1000 (bronchodilators), indomethacin, ACTH, cortisol and various synthetic corticosteroids. (three new concepts have to be considered: a. The Chronokinetic of a Drug. This term includes both rhythmic changes in the drug vioavailability, pharmacokinetic and its excretion. b. The Chronesthesy of a Biosystem to a Drug. i.e. circadian changes in the susceptibility of any biosystem to a drug. c. The Chronergy of a Drug, taking into consideration its chronokinetic and the chronesthesies of the involved organismic biosystems. Chronopharmacology is useful to solve problems of drug optimization, i.e. to enhance the desired effeciency or to reduce its undesired effects. In the human organism (among other animal species) the metabolic fate of a pharmacologic agent (as well as that of a nutrient) is not constant as a function of time. Thus, the chronobiologic approach of pharmacologic phenomena involves a lesser risk of errors and/or false information than the conventional homeostatic approach.