Chronopharmacology and antimicrobial therapeutics

Chronobiology studies the phenomenon of rhythmicity in living organisms. Circadian rhythms are genetically determined and are regulated by external synchronizers (i.e. light/day cycle). Several biological processes involved in the pharmacokinetics and pharmacodynamics of drugs are subject to circadian variations. Chronopharmacology studies how biological rhythms impact on drug pharmacokinetic (chronokinetics), pharmacodynamics (chronoesthesy) and toxicity and determines whether time of day administration modifies drug's pharmacological characteristics. Chronotherapy applies chronopharmacological studies to clinical treatments, determining the best biological time for its dosing, i.e. when beneficial effects are maximal and incidence and/or intensity of related side-effects and toxicity are minimal. Significant variations in the pharmacokinetics and toxicity of antibiotics (aminoglycosides, beta-lactams and fluoroquinolones) related to administration time are well known. The aims of this review are to discuss, briefly, the currently accepted model of the circadian system that substantiates endogenous rhythmicity and to provide an update on the knowledge of circadian rhythms applied to drugs used as medicines, with a special mention to the possible impact on antimicrobial treatments. It is concluded that the dosing time of an antimicrobial agent might be clinically relevant in some treatments, thus, clinicians should be aware that the dosing time might affect the clinical response of a drug.