Anesth Analg 2001;93:1626
© 2001 International Anesthesia Research Society
LETTERS TO THE EDITOR
Analgesic Efficacy of Tramadol if Coadministered with Ondansetron
Ulrike M. Stamer, MD, and
Frank Stüber, MD PhD
Department of Anesthesiology and Intensive Care Medicine, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany
To the Editor: In the article by De Witte et al. (1), cumulative tramadol consumption was larger in the ondansetron group compared with the placebo group.
Unfortunately, the authors did not adequately discuss this phenomenon in depth. The reason for this large tramadol consumption when coadministered with ondansetron probably involves the major pathways of metabolism both drugs have in common. The 5-hydroxytryptamine antagonist, as well as tramadol, are metabolized by cytochrome P450–2D6. Antinociceptive effect of the racemic mixture tramadol is a synergistic action of both enantiomers via µ-opioid receptors ((+)enantiomer) and norepinephrine reuptake inhibition ((-)enantiomer), respectively (2). Analgesic properties are maintained by the M1-metabolites. Their formation mainly depends on CYP2D6 activity.
However, CYP2D6 is also involved in the formation of the hydroxylated metabolites of ondansetron (3). Thus, coadministration of drugs competing for CYP2D6 influence the kinetics of ondansetron and tramadol and might probably be responsible for significantly larger doses of tramadol needed during the first postoperative hour. In contrast, during the later course of the study when the action of ondansetron given before induction of anesthesia dissipated, tramadol consumption did not differ between the ondansetron and placebo group.
Footnotes
Dr. De Witte does not wish to respond.
References
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De Witte JL, Schoenemaekers B, Sessler DI, Deloof T. The analgesic efficacy of tramadol is impaired by concurrent administration of ondansetron. Anesth Analg 2001; 92: 1319–21.[Free Full Text]
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Poulsen L, Arendt-Nielsen L, Bresen K, Sindrup SH. The hypoalgesic effect of tramadol in relation to CYP2D6. Clin Pharmacol Ther 1996; 60: 636–44.[Web of Science][Medline]
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Fischer V, Vickers AE, Heitz F, et al. The polymorphic cytochrome P-4502D6 is involved in the metabolism of both 5-hydroxytryptamine antagonists, tropisetron and ondansetron. Drug Metab Dispos 1994; 22: 269–4.[Abstract]
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