The Effect of CYP2D6 Gene Polymorphism on Tramadol Efficacy in Total Knee Arthroplasty

Background/Aim: Tramadol, a centrally acting analgesic, is widely used in postoperative pain management. This study investigates the relationship between CYP2D6 gene polymorphisms and the efficacy of tramadol in patients undergoing total knee arthroplasty. Patients and Methods: A total of 210 participants, including 110 TKA patients and 100 healthy controls, were enrolled. CYP2D6 genotyping was performed using PCR amplification and DNA sequencing. TKA patients received standard postoperative intravenous tramadol (100 mg), and pain intensity was assessed using the visual analogue scale (VAS) at 0, 15, 30, 45, and 60 minutes. Genotype-phenotype distributions and VAS time-course changes were statistically compared. Results: The extensive metabolizer (EM) phenotype was the most common in the patient group (78.2%). Significant correlations were observed between VAS score changes and CYP2D6*3 and *4 alleles. EM patients demonstrated superior analgesic response to tramadol compared to intermediate metabolizers. Docking results revealed strong binding affinities for tramadol and its metabolites to CYP2D6, ranging from −6.0 to −8.0 kcal/mol. Conclusion: The CYP2D6 genotype influences tramadol efficacy and side-effect profiles, suggesting that pharmacogenetic testing should guide postoperative pain therapy.