[Chronopharmacology and DDS (drug delivery system)]

Abstract

Rhythmic variations, including circadian and circannual ones, have been demonstrated in the pharmacokinetics and pharmacodynamics of many drugs. These suggest that the consideration of the timing of drug administration will improve rational drug therapy, increasing drug efficacy and safety. A drug delivery system (DDS) enabling a constant-rate administration is attractive from the clinical point of view, namely, such a system could minimize the peak and trough variation in plasma drug concentration after dosing so as to avoid toxicity associated with drug levels exceeding the upper limit of therapeutic range and lack of effect with drug levels dropping below the lower limit of the range. However, pulsatile administration is preferred for peptide and hormone pharmacotherapy. For chronopharmacotherapy, a pattern of input at different release rates is also preferred to that at a constant rate. These findings emphasize the need to consider chronopharmacology in DDS design.