Biological rhythms, drug delivery, and chronotherapeutics

Biological processes are highly structured in time as endogenously derived rhythms of short, intermediate, and long periods, with the circadian (24 h) time structure most studied. Staging of key physiological and biochemical circadian rhythms gives rise to 24-h patterns in the exacerbation of chronic medical conditions, including arthritis, asthma, ulcer, and hypertension, plus manifestation of acute severe morbid and mortal events, such as myocardial infarction, stroke, and sudden cardiac death. Body rhythms may also significantly affect patient response to diagnostic tests and pharmacokinetics, pharmacodynamics, and toxicities of diverse classes of medications. This chapter reviews circadian and other period biological rhythm dependencies of the pathophysiology of disease and pharmacology of medications as the basis for chronotherapeutics and development of time-modulated drug-delivery systems.