Chronopharmacological aspects in dose-concentration-response relationship.

概要

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In this review, rhythmic variations, including circadian and circannual ones, were demonstrated in the pharmacokinetics and pharmacodynamics of many drugs, These suggest that the consideration of the timing of drug administration improve a rational drug therapy, increasing drug efficacy and safety. Rhythmic variation in the dose-response relationship is caused by change in the dose-concentration and/or concentration-response relationship. Therefore, to investigate chronopharmacological study from viewpoints of dose-concentration-response relationship becomes an important clue for dosage adjustment. Controlled drug delivery systems are of great importance for the pharmacotherapy of disease, 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 peptides and hormone pharmacotherapy. For chronopharmacotherapy, a pattern of input at different release rates is also preferred to that at a constant rate. Finally, we emphasized the need to consider chronopharmacology in DDS design.
日本DDS学会の論文