The Associations Between CYP2D6*10 C188T Polymorphism and Pharmacokinetics and Clinical Outcomes of Tramadol: A Systematic Review and Meta-analysis

BACKGROUND: Tramadol is one of the most extensively used centrally acting synthetic opioid analgesics. Recently, a number of studies have explored the associations of the CYP2D6*10 C188T polymorphism with pharmacokinetic and clinical outcomes of tramadol. However, the results of these previous reports remain controversial. Therefore, a meta-analysis was needed to reach a consensus. METHODS: PubMed, EMBASE, and the Cochrane Library were searched to identify eligible studies that explored the influence of the CYP2D6*10 C188T polymorphism on clinical outcomes of tramadol through April 2019. Articles meeting the inclusion criteria were comprehensively reviewed by two independent evaluators. A meta-analysis was performed using Review Manager 5.3. RESULTS: A total of nine studies involving 809 related subjects were included in this meta-analysis. Significant associations were found between CYP2D6*10 C188T mutation and longer serum tramadol half-lives, larger AUC0-∞, and the slower clearance rate of tramadol. In addition, we also found that CYP2D6*10 C188T had effects on the pharmacokinetic parameters of the metabolite of tramadol, O-desmethyltramadol, by sensitive analysis. Furthermore, CYP2D6*10 C188T polymorphism was associated with higher visual analog scale score, loading dose, and total consumption of tramadol. There was no significant association between CYP2D6*10 C188T polymorphism and postoperative nausea and vomiting. CONCLUSIONS: CYP2D6*10 C188T polymorphism had a significant influence on tramadol pharmacokinetics and analgesic effect, but there was insufficient evidence to demonstrate that this polymorphism was associated with incidence of nausea and vomiting.