The metabolism of tramadol by human liver microsomes

Clin Investig. 1992 Aug;70(8):708-10. doi: 10.1007/BF00180294.


The metabolism of tramadol was investigated in vitro using microsomal fractions of human liver. The parent compound and its main metabolites were determined by a newly developed high performance liquid chromatography assay. O-demethylation of tramadol was found to be stereoselective. The Vmax of the O-demethylation of (-)-tramadol was 210, whereas (+)-tramadol was O-demethylated with a Vmax of 125 The Km for both enantiomers was determined to be 210 microM. O-demethylation was inhibited competitively by quinidine (ki = 15 nM) and propafenone (ki = 34 nM). N-demethylation was also stereoselective, preferentially metabolizing the (+)-enantiomer. Whereas O-demethylation displayed monophasic Michaelis-Menten kinetics, N-demethylation was best described by a two-site model. Competitive inhibition of the O-demethylation both by quinidine and propafenone suggests that O-demethylation is carried out by P-450IID6.

MeSH terms

  • Humans
  • In Vitro Techniques
  • Methylation
  • Microsomes, Liver / metabolism*
  • Tramadol / metabolism*


  • Tramadol