CIRCADIAN-RHYTHMS IN THE SUSCEPTIBILITY O F TARGET SYSTEMS TO DRUGS -AN UNDERESTIMATED PHENOMENON

The chronokinetics of a drug corresponds to dosing time-dependent and predictable (rhythmic) changes in parameters used to characterize its pharmacokinetics e.g. C-max, t(max), t(1/2), AUC, etc.) The chronesthe sy or chronopharmacodynamics corresponds to circadian changes in susce ptibility of target biosystems to this drug. The target system can be an organ or a tissue (skin, bronchial tree, etc.) as well as a recepto r, a membrane, an enzymatic process. Both theoretical and practical im plications of chronesthesy have been underestimated and even ignored. It is usually assumed that the constant level over time of a drug in t he plasma should result in constant effects. Much experimental, eviden ce have shown that this hypothesis must be rejected.