Circadian events in human diseases and in cytochrome P450-related drug metabolism and therapy

Authors

  • Rok Košir,

    1. Center for Functional Genomics and Bio-chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana Ljubljana, Slovenia
    2. DiaGenomi Ltd., Ljubljana, Slovenia
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  • Klemen Španinger,

    1. Center for Functional Genomics and Bio-chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana Ljubljana, Slovenia
    2. DiaGenomi Ltd., Ljubljana, Slovenia
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  • Damjana Rozman

    Corresponding author
    1. Center for Functional Genomics and Bio-chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana Ljubljana, Slovenia
    • Center for Functional Genomics and Bio-chips, Faculty of Medicine, University of Ljubljana Ljubljana, Slovenia
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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. © 2013 IUBMB Life, 65(6)487:–496, 2013.

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