Clinical chronopharmacology in the elderly.

The behavior and effects of medications may be modified in the elderly. Factors contributing to such alterations may involve differences in drug pharmacokinetics and response and/or social and economic factors that affect nutrition and compliance to medications. Many studies have been devoted to such factors, but most of them have not taken into account chronopharmacologic data. Indeed, drug-administration time constitutes an additional factor of variability in drug response in the elderly. Biological rhythm-dependent differences in the kinetics and dynamics of medications seem to be diminished or altered with aging. Chronopathological (rhythmic aspects of disease) data in the elderly are of particular importance, taking into account frequently associated diseases, such as chronic obstructive pulmonary disease, cancer, diabetes, glaucoma, hypertension, and inflammatory conditions, among others. Although some chronobiological data are available, chronopharmacologic phenomena have yet to be extensively investigated in the elderly. Most of the sparse studies concern drug chronokinetics, but the data found in the literature do not reveal a clear trend in the age-related changes. Chronokinetic variations in the elderly, compared to young adults, suggest an amplification of the administration-time effects, as demonstrated for digoxin; dampening, as demonstrated for indomethacin; or detection of administration-time effects only in aged but not in young subjects, as found for others medications. Additional studies are needed to better understand the influence of age on the chronokinetics of medications. Moreover, the literature on possible administration-time differences in drug dynamics in the elderly is also very sparse. Altered receptor and/or post-receptor properties and impaired sensitivity of homeostatic mechanisms have yet to be studied from a chronopharmacological point of view. Thus, additional studies are needed to properly understand how drug responses in the elderly may vary in relation to the circadian timing of medications.