title: The metabolism of tramadol by human liver microsomes.
abstract: 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 pmol.mg-1.min-1, whereas (+)-tramadol was O-demethylated with a Vmax of 125 pmol.mg-1.min-1. 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.
authors.affiliation: Zentrum für Innere Medizin-Allgemeine Innere Medizin, Universität Bonn.
authors.forename: W D
authors.initials: WD
authors.lastname: Paar
authors.forename: P
authors.initials: P
authors.lastname: Frankus
authors.forename: H J
authors.initials: HJ
authors.lastname: Dengler
mesh_terms: D006801:Humans; D066298:In Vitro Techniques; D008745:Methylation; D008862:Microsomes, Liver / Q000378:metabolism*; D014147:Tramadol / Q000378:metabolism*
chemical_list: D014147:Tramadol