Circadian Rhythm and Cytochrome p450 Enzymes

Circadian rhythm has an effect on the response of the metabolism, distribution, absorption and elimination kinetics of drug and xenobiotic metabolism through biochemical and physiological pathways of detoxification enzymes. Among those enzymes, cytochrome P450 enzymes (CYP-450); CYP2 (CYP2A1/4/5, CYP2B1/2/10, CYP2C6/50, CYP2E1), CYP3 (CYP3A4/11), CYP4A3, CYP8B7A, CYP9, CYP7, CYP17 and the transcriptional activators of these enzymes through nuclear receptors, such as pregnane-X receptor (PXR, NR112), constitutive adrostane receptor (CAR, NR113), peroxisome prolifera-tor-activated receptor alpha (PPAR), retinoic acid receptor (RAR), related orphan receptor (ROR) and RER-ERBα, have been shown to follow circadian rhytmicity in several studies. Melatonin which is metabolized by these hepatic CYP450 monooxy-genases, affects the biological clock and the regulation of these enzymes. Therefore, it could be stated that the circadian variation of these detoxification enzymes affects the availability and toxicity of drugs and xenobiotics which influence the chronotherapeutical and chronotoxicity approaches rather than the classical one, should also be considered in future experimental studies for obtaining more reliable outcomes.