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Omtrent 7-9 % af den kaukasiske befolkning har variationer i CYP2D6 genet som koder for ingen- eller nedsat aktivitet af CYP2D6 (se personlig medicin ). Tramadol et produg der omdannes til den aktive metabolit through CYP2D6. Patienter med nedsat eller manglende aktivitet af CYP2D6, vil have reduceret- eller manglende effekt af tramadol.Andre smert