Impact of CYP2D6 and CYP2B6 phenotypes on the response to tramadol in patients with acute post‐surgical pain

Tramadol is an important minor opioid prescribed for pain management. In this study, we analyzed the well‐known impact of CYP2D6 genetic variation and 60 additional variants in eight candidate genes (i.e., ABCG2, SLCO1B1, CYP2D6, CYP2B6, CYP2C19, CYP2C9, CYP3A5, and CYP3A4) on tramadol efficacy and safety. Some 108 patients with pain after surgery admitted to a post‐anesthesia care unit (PACU) and prescribed tramadol were recruited. They were genotyped, and tramadol M1/M2 metabolite concentrations were determined by a newly validated HPLC‐MS/MS method. CYP2D6 intermediate (IM) and poor (PM) metabolizers showed lower M1 concentrations adjusted for dose/weight at 30 and 120 min compared to ultrarapid (UM) and normal (NM) metabolizers (univariate p