OBJECTIVE: This study was designed to investigate whether the in vivo metabolism of tramadol was influenced by CYP2D6 polymorphism. METHODS: The extent of tramadol O- and N-demethylation was calculated by determining the amounts of tramadol and O- and N-desmethyltramadol in 24 h urine after ingestion of a test dose of tramadol. The O- and N-demethylation rates were calculated by dividing the 24-h urinary excretion amount of tramadol by that of O- and N-desmethyltramadol. Volunteers were phenotyped for CYP2D6 polymorphism using sparteine as an in vivo probe. RESULTS AND CONCLUSION: High correlation was found between tramadol-O-demethylation and sparteine oxidation in 71 extensive metabolizers of sparteine (rs = 0.544). The mean metabolic ratio of tramadol O-demethylation was significantly higher in poor metabolizers of sparteine than in extensive metabolizers (4.4 vs 0.8). These in vivo results confirm that tramadol O-demethylation is carried out to a large extent by the polymorphic CYP2D6.
OBJECTIVE: This study was designed to investigate whether the in vivo metabolism of tramadol was influenced by CYP2D6 polymorphism. METHODS: The extent of tramadol O- and N-demethylation was calculated by determining the amounts of tramadol and O- and N-desmethyltramadol in 24 h urine after ingestion of a test dose of tramadol. The O- and N-demethylation rates were calculated by dividing the 24-h urinary excretion amount of tramadol by that of O- and N-desmethyltramadol. Volunteers were phenotyped for CYP2D6 polymorphism using sparteine as an in vivo probe. RESULTS AND CONCLUSION: High correlation was found between tramadol-O-demethylation and sparteine oxidation in 71 extensive metabolizers of sparteine (rs = 0.544). The mean metabolic ratio of tramadol O-demethylation was significantly higher in poor metabolizers of sparteine than in extensive metabolizers (4.4 vs 0.8). These in vivo results confirm that tramadol O-demethylation is carried out to a large extent by the polymorphic CYP2D6.
Authors: Karel Allegaert; J N Van den Anker; R Verbesselt; J de Hoon; C Vanhole; D Tibboel; H Devlieger Journal: Eur J Clin Pharmacol Date: 2005-11-08 Impact factor: 2.953
Authors: Janet K Coller; Jennifer R Michalakas; Heather M James; Aaron L Farquharson; Joel Colvill; Jason M White; Andrew A Somogyi Journal: Br J Clin Pharmacol Date: 2012-11 Impact factor: 4.335
Authors: Nora M Hagelberg; Tuukka Saarikoski; Teijo I Saari; Mikko Neuvonen; Pertti J Neuvonen; Miia Turpeinen; Mika Scheinin; Kari Laine; Klaus T Olkkola Journal: Eur J Clin Pharmacol Date: 2012-10-26 Impact factor: 2.953