engleski

Systemic inflammation modulates postoperative tramadol metabolism towards inactive metabolites: a prospective observational study.

Introduction: Systemic inflammation can alter drug metabolism by inhibiting phase I metabolism enzymes. The aim of the study was to examine the effect of systemic inflammation on the tramadol metabolism in patients admitted to the intensive care unit (ICU). Methods: The study included 44 patients admitted to the ICU after major abdominal surgeries. CYP2D6 gene polymorphism was determined in all patients. Concentrations of CRP, PCT and plasma cholinesterase activity (ChE) were analysed from a blood sample of all patients before the surgery. Postoperatively, patients received 100 mg of tramadol intravenously every 6 hours. Tramadol, O- demethyltramadol (ODT), and N-demethyltramadol (NDT) concentrations were measured 6 times during the first 24 postoperative hours. Postoperative pain was measured before and after tramadol administration. Systemic inflammation was assessed based on clinical criteria in the postoperative period. Results: 22 patients were intermediate (IM) and 22 were extensive metabolizers (EM). After 400 mg of i.v. tramadol there was no differences in AUC1-24 of tramadol and NDT between metabolic phenotypes, median of 7320.4 (4671.5-10681.8) μg·h/L, and 448.8 (235.1-1135.7) μg·h/L. AUC1-24 of ODT were 1687.2 (930.6-2688.7) μg·h/L and 784.9 (469.1-1558.1) μg·h/L in EM and IM, respectively (P=0.009). Preoperative ChE ≤4244 U/L was a cut-off value for prediction of systemic inflammation. AUC1-24 NDT were higher in the patients with low ChE compared with normal ChE patients, 793 (397.2-1325.3) μg·h/L, and 357.8 (198.8-527.6) μg·h/L (P=0.02). Tramadol analgesia was effective in all patients regardless of ChE activity. Conclusion: CYP2D6 polymorphism is the most important factor in O- demethylation of tramadol, while systemic inflammation accompanied by low preoperative ChE activity is a significant factor contributing to N-demethylation of tramadol.

tramadol, metabolism, inflammation, intensive care

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