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Tramadol, alone or in combination with paracetamol, is an effective analgesic that relieves the moderate to severe pain that accompanies various disorders (including osteoarthritis) and follows surgical operations. However, this synthetic atypical opioid frequently evokes various adverse events (AEs), and the most frequent are nausea and vomiting.1 Although the mode of tramadol-induced nausea/vomiting is unclear, opioid receptors on the chemoreceptor trigger zone in the human brain can bind opioids to cause nausea/vomiting.2 A major pathway of tramadol metabolism is demethylation to O-desmethyltramadol by cytochrome P450 enzyme 2D6 (CYP2D6),3 and O-desmethyltramadol has an orders of magnitude higher affinity for the μ-opioid receptor (OPRM1) than tramadol and other metabolites.4
Because many genetic variations in CYP2D6 confer large interindividual differences in enzyme activity,5 and several variations in OPRM1 substantially affect expression level,6 this study examined genotype–phenotype associations between functional polymorphisms in CYP2D6 …
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