European Journal of Clinical Pharmacology

, Volume 53, Issue 3, pp 235–239

Polymorphic CYP2D6 mediates O-demethylation of the opioid analgesic tramadol

  • W. D. Paar
  • S. Poche
  • J. Gerloff
  • H. J. Dengler
PHARMACOKINETICS AND DISPOSITION

DOI: 10.1007/s002280050368

Cite this article as:
Paar, W., Poche, S., Gerloff, J. et al. E J Clin Pharmacol (1997) 53: 235. doi:10.1007/s002280050368

Abstract

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.

Key words Tramadol CYP2D6 

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • W. D. Paar
    • 1
  • S. Poche
    • 1
  • J. Gerloff
    • 2
  • H. J. Dengler
    • 1
  1. 1.Department of General Internal Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn-Venusberg, Germany Tel. +49228/2875507; Fax +49228/2874323DE
  2. 2.Department of Clinical Pharmacology, Grünenthal GmbH, Aachen, GermanyDE