Biological rhythms: a neglected factor of variability in pharmacokinetic studies.

Biological rhythms may influence drug response (chronopharmacology) and some chronopharmacological studies have underlined the influence of time of day on drug pharmacodynamics and pharmacokinetics. The aim of the present review is to underline how biological rhythms may interfere with drug kinetics and to try to underline when, how, and why taking into account the moment of administration of a drug. Many physiological factors, possibly implicated in different steps of the fate of drugs in the organism (e.g., absorption, distribution, metabolism, and elimination) vary along the 24 h scale. Taking into account biological rhythms in kinetic studies, should be indicated when the concerned drug will be used in a chronobiological disease (e.g., asthma, cancer, depression, hypertension, gastrointestinal diseases, rheumatisms), etc. In case of a drug characterised by a high inter- and intra-variability, a narrow therapeutic range or when the drug will be further used following a once-a-day formulation. It is of importance to rigorously control factors which are known to influence pharmacokinetic processes in chronokinetic studies. Time of day has to be regarded as an additional variable to influence the kinetics of a drug.