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 CYP2D610 C188T mutation and longer serum tramadol half-lives, larger AUC0-∞, and the slower clearance rate of tramadol. In addition, we also found that CYP2D610 C188T had effects on the pharmacokinetic parameters of the metabolite of tramadol, O-desmethyltramadol, by sensitive analysis. Furthermore, CYP2D610 C188T polymorphism was associated with higher visual analog scale score, loading dose, and total consumption of tramadol. There was no significant association between CYP2D610 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.