The knowledge of 24 hr rhythm in the risk of disease plus evidence of 24 hr rhythm dependencies of drug pharmacokinetics, eŠects, and safety constitutes the rationale for pharmacotherapy (chronotherapy).20) One approach to increase the e‹ciency of pharmacotherapy is the administration of drugs at times at which they are most eŠective andWor best tolerated. The chronotherapy of a medication may be accomplished by the appropriate timing of conventionally formulated tabletes and capsules, and a special drug delivery system to synchronize drug concentrations to rhythms in disease activity. Chronotherapy is especially relevant in the following cases. The risk andWor intensity of the symptoms of disease vary predicably over time as exempliˆed by allergic rhinitis, arthritis, asthma, myocardial infarction, congestive heart failure, stroke, and peptic ulcer disease. The therapeutic-to-toxicity ratio of a medication varies predictably according to chronobiological determinants as exempliˆed by antitumor medications. The pharmacokinetics and pharmacodynamics of a medication vary depending on biological rhythms. The goal of pharmacotherapy is hormonal substitution to mimic the rhythmic variation of hormone levels in healthy individuals. Also on the horizon are drugs to ˆx broken biological clocks, perhaps a factor in all illness in the opinion of some physicians. Table 1 shows several examples of chronopharmacotherapy.21)
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