[Mechanisms and perspectives in clinical chronopharmacokinetics]

The pharmacokinetic parameters of drugs vary largely and predictably as a function of their dosing time along the 24-hr scale (and also the year and the menstrual cycle) in Man. Such chronopharmacokinetics have been described following single or repeated doses via the oral or the venous route, and whether drug halflife is short or long. Moreover continuous infusion of a drug at a constant rate cannot maintain constant plasma levels. Such phenomena are accounted for by circadian (and other) rhythms which characterize absorption, protein binding, transmembrane flux, as well as liver and kidney metabolism and biliary and urinary excretions. It is anticipated that the knowledge of the physical and chemical properties of a drug and that of the circadian organization of the main physiologic functions involved into its bioavailability will allow to predict its chronopharmacokinetics.