title: Circadian events in human diseases and in cytochrome P450-related drug metabolism and therapy.
abstract: The biochemical basis of the mammalian circadian clock can be described by transcriptional-translational feedback loops with a period of about 24 h. Crucial endogenous factors are under circadian control (i.e., body temperature, blood pressure, hormone secretion and metabolite levels). Also, drug metabolism, including phases I-III and the drug-responsive nuclear receptors, is controlled by the clock. Disturbances in circadian rhythm in humans can lead to pathologies, which is exemplified by increased cancer risk in long-term shift workers. On the other hand, best tolerability of drugs with minimum side effects can be achieved if the timing of drug treatment is synchronized with the patients' individual clock. The aim of this review is to underline the importance of accepting the individuals' endogenous clock which can contribute to personalized, patient-friendly optimization of drug therapies.
authors.affiliation: Center for Functional Genomics and Bio-chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana Ljubljana, Slovenia.
authors.forename: Rok
authors.initials: R
authors.lastname: Košir
authors.forename: Klemen
authors.initials: K
authors.lastname: Španinger
authors.forename: Damjana
authors.initials: D
authors.lastname: Rozman
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001249:Asthma / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000188:drug therapy; D002940:Circadian Rhythm; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D055870:Drug Chronotherapy; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008658:Inactivation, Metabolic / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D013276:Stomach Ulcer / Q000188:drug therapy
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D003577:Cytochrome P-450 Enzyme System
keywords: complex diseases; drug design; hemeproteins; transcription factors; transcriptional regulation